Oncolix, Inc. (Oncolix) is a clinical-stage bio-pharmaceutical company based in Houston, Texas. The company is developing Prolanta™, a targeted therapeutic protein for the treatment of ovarian, breast and other cancers. Prolanta™ is an antagonist of the human prolactin receptor, blocking the effects of human prolactin. There is substantial scientific evidence that human prolactin is associated with the growth of certain cancers as well as resistance of cancers to platinum and taxane therapies. By blocking the effects of prolactin, Prolanta™ has demonstrated a high level of efficacy in ovarian and breast cancer models, and is also expected to be effective in models of other cancers.
The U.S. FDA has cleared our Investigational New Drug (IND) application to commence human testing of Prolanta™ for the treatment of ovarian cancer, which is our first indication. This Phase I clinical trial commenced in early 2016. The FDA has also granted Prolanta™ Orphan Drug status, which may allow for accelerated regulatory approval, reduced filing fees, federal tax credits and marketing exclusivity.
Human prolactin is mainly synthesized and secreted by lactotroph cells in the anterior pituitary gland, but is also produced at sites outside the pituitary gland, such as the mammary gland, ovary, uterus, prostate, lymphocytes, brain, and several types of tumor cells. This extra-pituitary prolactin can act as a tumor growth factor in an autocrine-paracrine fashion, both on the tumor cells that secrete prolactin (autocrine) as well as on nearby cells (paracrine).
Human prolactin binds with its cell surface receptor through dimerization, activating various proliferation and chemo-resistance pathways. Our drug Prolanta™ is an analogue to prolactin, with a single amino acid substitution mutation at position 129 to create a receptor-specific antagonist (also referred to as G129R). This glycine to arginine substitution interferes with the binding of the mutated ligand at the second receptor site, thereby disrupting dimerization of the receptors necessary for activation.
As illustrated in the following figure, prolactin binds to two receptors and initiates various growth pathways, the most well known of which is the Jak2/STAT pathway. When Prolanta™ (G129R) binds to the receptor, it blocks prolactin from starting this pathway. Additionally, our collaborators at MD Anderson Cancer Center have discovered that Prolanta™ can also initiate a cell death pathway, known as autophagy. The prolactin receptor is expressed in the majority of ovarian and breast cancer patients, and a prolactin receptor antagonist such as Prolanta™ is a novel candidate for the development of a targeted therapy for these cancer.