LOR-253 represents a new class of anticancer agent, which we believe may offer a competitive advantage over conventional drugs. This drug candidate has shown selective and potent antitumor activity in preclinical investigations with a variety of human cancers, including colon cancer and non-small cell lung cancer, and has demonstrated an excellent therapeutic window due to its low toxicity. LOR-253 is a first-in-class small molecule that has been optimized to induce the novel tumor suppressor Krüppel-like factor 4 (KLF4). Decreased expression of KLF4 has been demonstrated in several cancer types including non-small cell lung and colon cancers. Consistent with the tumor suppressor activity of KLF4, it expression suppresses cancer cell proliferation, induces apoptosis and inhibits metastasis. In addition, gene expression analysis in tumors treated with LOR-253 was notable for rapid and sustained KLF4 gene expression. The first-in-human Phase I study of LOR-253 was initiated to investigate the maximum tolerated dose (MTD) or target-relevant dose, safety and preliminary indications of efficacy.
This 27-patient study, conducted at Memorial Sloan Kettering Cancer Center in New York and the MD Anderson Cancer Center in Houston, has successfully escalated to the target dose level based on predicted and observed clinical effects without limitation by toxicity. The success of this study allowed Lorus to initiate a biomarker study in Jan 2013 to further explore the effects of the drug at relevant doses determined in the clinical trial. This biomarker study will enroll 10 patients eligible for pre- and on-treatment biopsies who have specific cancers prioritized for further clinical development of LOR-253. The objective of this biomarker study is to determine if LOR-253 is achieving antitumor activity through the elevation of KLF4 in tumors isolated from patients with primarily colon and non-small cell lung cancer. Results of this biomarker study are expected in the second half of the year. A Phase II protocol is being developed in consultation with thought leaders in the field and likely cancers to be targeted include non-small cell lung and colon cancer.
First-in-class small molecule drugs similar to LOR-253 are highly desirable in-licensing targets and have in the past achieved attractive partnership deals with substantial upfront and milestone payments and double-digit royalties for licensors. Indications that are experimentally promising and highly target-relevant for LOR-253 are NSCLC, colorectal cancer, and acute myeloid leukemia (AML), all cancers with high unmet medical need. LOR-253 represents a novel approach to therapy in these otherwise hard-to-treat cancers. We believe the market for LOR-253 in solid tumors could be in excess of $3 billion p.a.