A novel platform for targeted radiopharmaceuticals for imaging and therapy of ovarian cancer

Project Summary The goal of this Phase I STTR is to continue development of Oncurie’s novel ovarian cancer targeting compound, which binds to the folate receptor and delivers radionuclides suitable for targeted imaging and therapy with a proprietary moiety. The disease is difficult to detect in early stages with an estimated 75% of

women presenting with advanced disease at the time of diagnosis. The mortality rate of ovarian cancer is one of the least improved in recent years, with 5-year survival rates for stage III and stage IV disease estimated at 42% and 26%, respectively. These factors highlight the urgently unmet need for new diagnostic tools and therapeutic

strategies for this devastating disease which impacts over 20,000 women per year in the US, resulting in approximately 14,000 deaths. Oncurie has developed a targeted radiopharmaceutical platform enabling precision imaging of ovarian cancer with future developments towards therapy. The compound includes two key

features: 1) a folate receptor (FR) binding moiety to exploit the receptor’s well-documented overexpression in ovarian cancer; and 2) Oncurie’s proprietary radionuclide-binding domain which binds radioisotopes with high affinity preventing in vivo dissociation from the core compound resulting in improved safety and targeting efficacy.

In collaboration with Suzanne Lapi, PhD of the University of Alabama at Birmingham, the company has shown that the compound (O5) binds ovarian cancer cells with sub-nanomolar affinity and is internalized to the nucleus. In vivo, O5 has been shown to specifically target the folate receptor present on ovarian cancer tumors in

xenograft models. During Phase I, we will refine the molecular structure and formulation of the compound to improve synthetic scalability, ease of handling and ensure radiolabeling chemistries remain reliable and efficient. In vitro testing will be undertaken to confirm the compound’s FR-targeting properties in a range of ovarian cancer

cell lines. Finally, the compound will be evaluated in a patient-derived xenograft (PDX) model of ovarian cancer, which more closely resembles human disease pathogenesis compared to the xenograft model used for initial proof-of-concept studies presented in the Preliminary Data section. Pending successful completion of these

Phase I Aims, a subsequent Phase II program will advance the compound through critical safety, toxicology, and efficacy testing required for submission of an Investigational New Drug (IND) application to the FDA to enable clinical studies. It should also be noted that, while Oncurie’s current strategy is to evaluate this compound for

radiographic imaging and disease diagnosis, the same compound is intended to be used as a therapeutic when paired with a cytotoxic radionuclide as part of a theranostic strategy. Currently marketed radiotherapeutics such as Lutathera and Pluvicto employed a similar strategy, developing a diagnostic imaging agent first, followed by

the development of a therapeutic with effectively the same core molecule. Oncurie’s product is estimated to have similar revenue potential compared to these products, reportedly ranging from $500 million to $1 billion.