Current limitations of Radiation Therapy
Radiation oncology has been a mainstay for the treatment of cancer malignancies for more than half a century. The combination treatment of radiation therapy and chemotherapy has involved the use of cytotoxic, targeted biologic agents and targeted external beam radiation to increase the destruction of tumor cells and cure or delay progression of the cancer, improving patient survival and quality of life. The low number of drugs and biologic agents under investigation as radiation sensitizing agents indicates an unmet need for new approaches and agents that provide greater efficacy, increased safety and better tolerability for patients.
Currently, “chemo-radiation” treatments are well established in cancers of the head and neck, esophagus, lung, stomach, breast, brain, pancreas, rectum and uterine cervix. The ideal radiation sensitizer would reach the tumor in adequate concentrations and act selectively in the tumor compared to the surrounding normal tissue. It would have predictable pharmacokinetics for timing with radiation therapy and could be administered with every radiation treatment approach. The ideal radiation sensitizer would have minimal toxicity or manageable enhancement of radiation therapy.
Shuttle's Revolutionary Solutions
Drawing on the research experience of Shuttle founders in drug discovery and development, a rational drug design strategy was initiated to discover molecules capable of sensitizing cancers to radiation therapy while protecting normal tissues from radiation injury. Halogenated thymidine analogs, nitroimidazole nucleoside analogs and inhibitors of histone deacetylases (HDACi) provided platform technology for design of novel small molecules, leading to company owned intellectual property.
Our HDAC platform technology is developing a pipeline of products designed to address the limitations of the current standard of cancer therapies. Because our proprietary technology activates the DNA damage response and expression of immune modulating proteins, they affect cancer cell killing by radiation and by the immune system. As a result of this, we are exploring our novel technology with immunotherapies such as checkpoint inhibitors. We have demonstrated proof of concept of our HDAC platform in preclinical models for a number of diseases and are focused on developing this technology for solid tumor cancers. In addition, we have included in our portfolio of products clinical-stage products that complement our overall vision to cure cancer using novel therapies in conjunction with radiation therapies. We utilized non-dilutive SBIR contracts to advance the radiation sensitizer Ropidoxuridine through a phase I clinical trial, we have signed a licensing agreement with the University of Virginia to develop and commercialize Heavy Oxygen IPdR, a proprietary approach for a proton specific radiation sensitizer, and have in-licensed the hypoxic radiation sensitizer Doranidazole for clinical testing in the US from Pola Pharma.