SMALL MOLECULE DRUG DISCOVERY AND DEVELOPMENT
For Unmet Medical Needs
MD2 Biosciences is a Delaware-C-corporation, founded in October 2015, headquartered in San Diego. MD2 utilizes the expertise of cancer biology, Q-MOL computational platform technology, and medicinal chemistry to develop opportunities for cancer. Targeting ‘Transcription Factors’ to discover and develop small molecule drugs using ‘Platform Technology for unmet medical needs such as colorectal cancer and other cancers.
Globally, colorectal cancer (CRC) is the third most common type of cancer, making up about 10% of all cases. In 2012, there were 1.4 million new cases and 694,000 deaths from CRC. Chemotherapies including oxaliplatin, irinotecan, and fluorouracil are widely used to treat the advanced disease. Therapies against vascular endothelial growth factors (VEGF) or their receptors, such as bevacizumab, aflibercept, and regorafenib, prolong survival of patients with advanced CRC. Despite advances in surgical resection, and systemic therapies, including adjuvant chemotherapies, many patients still die of CRC, and third in cancer-related deaths worldwide. Therefore, therapies that can cure CRC will have a significant societal impact.
Approximately 90% of sporadic CRCs contain mutations in components of the Wnt/ b-catenin signaling[i] pathway. These mutations are found in the earliest neoplasms suggesting that this pathway serves as a critical gatekeeper to prevent colorectal carcinogenesis. Most tumors contain a mutation in a single component of the pathway, although recent data from the cancer genome atlas consortium indicates that mutations in multiple components can co-occur. The majority of mutations, some 85%, map to ‘hotspots’ within APC and often lead to expression of a truncated APC protein from this allele. This truncated protein is incapable of incorporating into a function b-catenin destruction complex. Thus, when the wild-type APC is inactivated by mutations or lost through loss of heterozygosity, b-catenin levels inappropriately accumulate in the cell, leading to an aberrant expression of Wnt/b-catenin targeting genes and the development of benign adenomas. As these adenomas accumulate additional mutation in other signaling pathways, they transition into carcinomas. Therefore, CRC is a disease of Wnt/b-catenin signaling, where b-catenin/TCF complexes bound to Wnt-responsive DNA elements driving pathogenic expression targeting genes. The available standard of care agents therapy is limited to WT cancer cells and not for mutant cancer cells. Additionally, the standard of care agents is known to cause irreversible side effects to patients such as chemotherapy-induced peripheral neuropathway, etc. At MD2, we are specifically targeting b-catenin directly to treat both WT and mutant cancer cells with our small molecule drugs. Our direct b-catenin inhibitors target b-catenin in the cytoplasm and thus reduce burden in the nucleus.