Photolitec's patented technology is focused on developing improved agents for tumor- imaging, image-guided surgery and/or photodynamic therapy (PDT). The proposed STTR proposal includes fluorescence-image guided PDT, a "See and Treat" approach. The fluorescence imaging compound with long wavelength absorption near 800 nm should be extremely useful for image-guided therapy (PDT alone or surgery + PDT) for treating a variety of tumors, especially large and deeply seated tumors. Due to its non-radioactive nature, the fluorescence tomography, currently being explored for human use, will have a significant impact in tumor diagnosis. In summary, such compounds can be used for tumor detection, monitoring the tumor response, assessing disease and image-guided therapy. The NIR photosensitizer (PS) technology developed at Roswell Park Cancer Institute (RPCI) is transferred to Photolite, LLC (a spin-off company of RPCI) is highly effective, exhibit a large Stokes shift and does not show any significant toxicity. Therefore, the success rate for further development is high. Due to the presence of a chiral center at position-3, the bacteriochlorin-based PS (787 nm), it exists as a mixture of R- &S- isomers in a 1:1 ratio. The in vitro/in vivo PDT efficacy of both the isomers was similar to the parent PS (isomeric mixture) without any significant skin phototoxicity, a major drawback associated with most of the porphyrin-based PS [e.g. Photofrin and m-THPC (Foscan)]. However, a detailed Pharmacokinetics (PK)/ Pharmacodynamics (PD) of the PS as an isomeric mixture or as a pure R- and S- isomers has not been investigated. On the basis of limited preliminary results, it is not yet clear whether to pursue the development of the isomeric mixture or the individual isomers. Therefore, the Phase I/II study has been divided in two parts: Phase I: (a) To use the treatment parameters of NIR PS and its stereoisomers (R- &S-) already established in mice bearing Colon26 tumors to brain (U87, Gl261, 9L) and head &neck (SCC) tumors and investigate its utility in fluorescence-imaging and PDT (b) To investigate normal organ toxicity of the PS and its stereoisomers in mice and (c) Have a meeting with FDA, select the PS and plan toxicological studies for Phase II studies accordingly. Phase II: (a) To use the GMP manufactured PS, formulated in a GLP facility for PDT efficacy in the selected tumor model (Phase I) at variable light dosimeter, (b) To investigate toxicity and PK/PD studies of the PS in two animal species following the US FDA requirements and finally, (c) Submit the application to FDA for Phase I human clinical trials.
The proposed fluorescence image-guided photodynamic therapy with NIR photosensitizers (near 800 nm) should help to image the tumor/tumor-margins with enhanced efficacy, survival and improved quality of life to cancer patients. The proposed fast track Phase I/II STTR proposal is aimed to compare the PDT and toxicological efficacy of the stereo isomers R- and S-) with the parent molecule and select the best isomer for Phase I human clinical trials of either head &neck or brain cancer.