Small Molecule Platform
Lorus has developed a group of potent small molecule compounds that are promising drug candidates for cancer therapy and have potential to be “first in class”. Lorus’ research scientists and medicinal chemists use structure-based drug design to derive compounds that target important proteins and therapeutic pathways in cancer. We have used this method to identify several groups of novel small molecules that show strong anticancer activity and a high therapeutic index due to low toxicity. Lorus has produced a series of advanced product candidates at discovery to preclinical development stages. In addition to the highly promising cancer applications, we have identified other therapy areas for which these compounds may be useful based on the mechanism of action, which could significantly expand the commercial potential of these molecules in the future.
LOR-253
LOR-253 (formerly LT-253) is the Company’s lead anticancer small molecule drug. LOR-253 is a first-in-class inhibitor of the Metal Transcription Factor-1 (MTF-1) with a novel mode of action. This consists of the induction of the tumor suppresor factor Krüppel like factor 4 (KLF4) leading to the downregulation of cyclin D1, an important regulator of cell cycle progression and cell proliferation, and decreased expression of genes involved in tumor hypoxia (low oxygen content) and angiogenesis. Increased angiogenesis and alterations in the cyclin D1 regulatory pathway have been linked to the development of cancer.
LOR-253 has selective and potent antitumor activity in a variety of human cancers, including colon and non-small cell lung cancer, and has demonstrated an excellent therapeutic index in experimental models. We have successfully completed GLP, IND-enabling toxicology studies for LOR-253, which included maximum tolerated dose (MTD) studies and repeat-dose toxicity studies in rodents and nonrodents. A Phase I dose escalation clinical trial to establish MTD and expansion at the MTD to evaluate intratumoral correlates of activity is expected to start by Q2 2010.
LOR-264
In addition to LOR-253, Lorus has developed an orally active second-generation derivative of this compound, LOR-264. Like LOR-253, LOR-264 has demonstrated potent anticancer activity in animal studies and represents the lead oral drug in this development platform. Derivatives of LOR-264 are currently being assessed for anticancer activity and oral bioavailability as part of our lead optimization process.
LOR-220
LOR-220 is a novel small molecule that targets a class of novel bacterial serine/threonine kinases, which has recently emerged as critical signaling molecules in bacteria. LOR-220 is active against multi-drug resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and other infections produced by important emerging pathogens. In preclinical studies, LOR-220 has demonstrated strong antimicrobial activity in animal models of sepsis without significant toxicity. A field study conducted with hundreds of clinical bacterial isolates demonstrated higher antimicrobial activity of LOR-220 compared with approved first line antimicrobial drugs.