Selection of Lead Candidate QBI-139 — More than thirty EVade™
RNases were manufactured and tested in vivo against
a variety of cancers. QBI-139 is a variant of human pancreatic RNase 1 that retains 95% sequence identity to the native protein, yet is able to kill cancer cells. QBI-139 was selected because of its broad
efficacy and excellent safety profile. In xenograft models, QBI-139 causes significant (>50%)
tumor growth inhibition in breast, colorectal, non-small cell
lung, ovarian, pancreatic and prostate cancers. Following large scale production, IND-enabling toxicology studies were completed and an Investigational New Drug (IND) application was submitted to the Food and Drug Administration
paving the way for a first in human Phase 1 clinical trial.
Phase I Trial of QBI-139 — A Phase I trial of QBI-139 in refractory patients with solid tumors is ongoing at University of Texas M. D. Anderson Cancer Center and University of Wisconsin Carbone Cancer Center. The Phase I trial of QBI-139 is a standard 3+3 dose escalation trial with a starting dose of 3 mg/m2. The drug was well tolerated in the most recent closed cohort (67 mg/m2). Analysis of adverse events, pharmacokinetics and immunogenicity is ongoing through dose escalation. Identification of the recommended Phase II dose is anticipated in the second half of 2012.
Competitive Advantages — To date, the data support the use of QBI-139 as a broadly effective anti-cancer agent with a good therapeutic window. While tumor growth inhibition greater than fifty percent was seen in a variety of xenograft models, toxicities commonly associated with chemotherapy have not been seen in non-clinical studies. These features position the drug well relative to traditional chemotherapy and targeted therapies.
Market — While QBI-139 has shown broad efficacy in model systems, the next stage of development requires narrowing the focus of the development efforts. Review of QBI-139 data, regulatory approaches and market factors has led to identification of ovarian and non-small cell lung cancer as areas where a drug with this profile could fill an unmet medical need.