This resubmission seeks to develop and establish our optical imaging agent, PARPi-FL, as a new drug for margin assessment of high grade dysplasia and cancer of the cervix and vulvar. This new technology will allow non-destructive and instant intraoperative margin assessment of surgically excised vulvar and cervical dysplasia specimens and early vulvar and cervical cancers. So far, well-established screening technologies, such as the Pap smear, have helped to reduce the mortality rate for cervical cancer by 50% over the last four decades in the United States. Positive Pap smears usually lead to interventions such as a loop electrosurgical procedure (LEEP). These LEEPs, however, can only rely on simple acetic acid to generate a visual contrast between healthy and cancerous tissue. Intuitively, this contrast is frequently weak and unreliable, resulting in imperfect interventions that ultimately lead to cancer recurrence. Repeated LEEPs also result in cervical scarring, increasing the risk of preterm delivery?a significant issue for the LEEP patient population of childbearing age. In the current resubmission, Summit Biomedical Imaging (SBI) will use its unique drug, which is currently being evaluated in a phase I clinical trial as an intraoperative imaging agent for oral cancer at Memorial Sloan Kettering Cancer Center (MSK), to non-invasively and non-destructively determine if the margins of cervical cone specimens, cervical loop electrical excisions, and vulvar excisions are negative or positive at the time of the surgical procedure. This project will serve as a proof-of-principle study to optimize staining for identification of disease, validate methodology, and choose the best imaging microscope setup for margin detection. We will also conduct a blinded margin assessment study, overseen by the Department of Epidemiology & Biostatistics at MSK, where we will determine positive predictive values (PPV) and negative predictive values (NPV) of our technology. For this study, we have brought together an interdisciplinary team of experts to facilitate the translation of this new biomedical imaging technology to the clinic. Dr. Christian Brand (CEO and molecular imaging expert) will manage the efforts at SBI. The MSK research team will comprise Dr. Thomas Reiner (probe development and laboratory analytics), Dr. Elizabeth Jewell (gynecological surgeon), and Dr. Snehal Patel (oral cancer surgeon and intra-operative imaging expert). Together, they form an ideal team to pursue this novel research avenue and represent expertise from a wide variety of disciplines. If successful, this study will form the basis of an SBIR phase II proposal, in which SBI will focus on clinical translation by initiating a phase I/II clinical study in concert with MSK.
This resubmission describes the evaluation of a diagnostic tool for margin assessment of high grade dysplasia and cancer of the cervix and vulva. Targeting the overexpression of PARP1, SBI's imaging agent, PARPi- FL, will be used as a non-invasive and non-destructive intraoperative imaging agent. The main objectives of our proposal are to optimize staining of disease, validate methodology, and select the best imaging microscope setup for margin detection in fresh human biospecimens of cervical high grade dysplasia and cancer of cervix and vulva.
