Commercialization of Algorithmic Non-thermal Ablation Technology for the Treatment of Inoperable Tumors

Project Abstract An estimated 320,000 patients are diagnosed with primary lung, liver, or pancreatic cancer per year. Unfortunately, the vast majority of these patients are not candidates for surgical resection, which is the only reliably curative treatment, yielding a five-year survival rate of approximately 10 to 20% for patients with primary disease. The primary clinical challenge is that most tumors form deep within organs, near major blood vessels, cardiac structures, bile ducts, or nerves which complicate surgical removal and contraindicate other first line treatments. Current focal ablation technologies on the market kill tissue at the cost of thermal heating around the treatment zone, thus cannot be performed near critical structures. Integrated-Time Nanosecond Pulse Irreversible Electroporation (INSPIRE) is a novel minimally invasive technique developed by the Gradient Medical for the treatment of inoperable tumors which uses ultrashort high intensity electrical pulses to destabilize the cell membrane and induce a tunable combination of necrotic and apoptotic cell death. We have demonstrated that this is a safe and effective cancer treatment in over 150 veterinary oncology cases and validated the reproducibility of INSPIRE in over 70 large animal models. In this proposal we will broaden the potential market for INSPIRE and advance the commercialization of the technology platform through four specific aims: 1) Development of a Commercial INSPIRE Pulse Generator. 2) Formative Usability with Refinement of Electrodes and Algorithms. 3) Pre-clinical Safety Study in High Need Scenarios. and 4) Assessment of Anti-Tumor Efficacy and Immunological Responses in a Canine Model. In the proposed study Gradient Medical will partner with an ISO 13485:2016 certified and 21 CFR Part 820 compliant medical device firm to transition our novel pulse generation system into a certified Quality Systems Management program. Gradient will further refine their applicator design through human factors and usability analysis to address issues discovered in Phase I (i.e. Temperature control overshoots and ultrasound visualization) and validate refinements to their novel temperature control algorithms. The safety of INSPIRE directly adjacent to critical structures (heart, major vessels, stroma) will be investigated via a collaboration with the NCSU College of Veterinary Medicine. A veterinary clinical trial in canine patients with large spontaneous hepatobiliary tumors will be used to validate the ability of INSPIRE treatments to address patients with late- stage disease and further broaden the potential market for the technology platform. The results from these studies will be used in relevant FDA approval submissions in preparation for first-in-human studies.