Image-guided Surgical Detection of Metastatic Disease to the Peritoneum

Summary (application predicated on NIH NCI Phase II 5R44CA217528-03): Surgical resection is a common front-line treatment for cancer that relies heavily on the surgeon’s ability to identify disease preoperatively and intraoperatively. While typical standard of care (SOC) preoperative diagnostics such as PET, CT, ultrasound, and MRI afford the surgeon critically important tools, they suffer from limitations associated with sensitivity and specificity that are critical to the intraoperative setting. Thus, the surgeon must rely on subjective visual and palpable cues during surgery which are subjective and often result in residual disease and positive surgical margins. Minimally invasive endoscopy and robotic surgeries further challenge the optics and haptics available to surgeons. Disease left behind leads to poorer patient outcomes (second surgeries, inaccurate sorting/staging for chemo and radiation therapy) and ultimately an increased burden on the healthcare system – all of which point to a significant unmet need. Approximately 70,000 peritoneal metastasis (PM) diagnoses have been made in 2020 alone. Patient prognosis from front line SOC cytoreductive surgery in conjunction with chemotherapy (such as hyperthermic intraperitoneal chemotherapy) or radiotherapy is dependent on completeness of removal of lesions that are small in size and heterogeneous in their oncogenic phenotype - especially challenging for the pre- and intraoperative detection modalities noted above. To address this unmet need, OncoNano Medicine has developed pegsitacianine (ONM-100), a single-dose IV administered imaging agent that utilizes pH as a universal biomarker for cancer to assist the surgeon during resection of solid tumors, regardless of their oncogenic phenotype. Safety and efficacy have been established in highly successful Phase 1 and Phase 2 trials for tumor detection, both primary and residual, and results are similarly encouraging for a nearly completed Phase 2 trial for PM that will form the indication for commercial launch. Realization of the value of pegsitacianine lies in a tumor-agnostic label claim that would encompass metastatic disease in the peritoneum regardless of primary tumor origin, providing an incredibly powerful and singular solution with significant potential that does not exist commercially. The noted heterogeneity in PM is expected to provide a pathway to substantiate FDA approval of a tumor-agnostic label. Investors and potential commercial partners (camera suppliers) who work with OncoNano in our clinical trials recognize the importance, value, and challenges of detecting peritoneal metastases and are actively engaged in pegsitacianine progress. However, their commitment to trigger private financing required for commercialization is predicated on demonstration of a de-risking clinical study. Critical to bridging this “valley of death” is the use non-dilutive funding from this grant as well as matching funds that have already been procured. The focus of this SBIR Phase IIB proposal is to conduct a pivotal Phase 3 study to generate a definitive data set to advance discussions with potential strategics and investors and obtain regulatory approval for pegsitacianine for metastatic disease in the peritoneum regardless of primary site of tumor origin.