Celsion announced the randomization of the first two patients in the Phase II portion of the Phase I/II OVATION 2 Study with GEN-1 in advanced ovarian cancer. The Company anticipates completing enrollment of up to 118 patients in the third quarter of 2021. Because this is an open-label study, the Company intends to provide clinical updates throughout the course of treatment including response rates and surgical resection scores.

GEN-1 was designed using TheraPlas, Celsion's proprietary, synthetic, non-viral nanoparticle delivery system platform. It is an interleukin-12 (IL-12) DNA plasmid vector associated with a non-viral nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein.

The OVATION 2 Study combines GEN-1 with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three adjuvant cycles of chemotherapy and up to nine additional weekly GEN-1 treatments, the goal of which is to delay progression and improve overall survival. The OVATION 2 Study is an open-label, 1-to-1 randomized trial, 80% powered to show the equivalent of a 33% improvement in progression-free survival (PFS) (HR=0.75), the primary endpoint, when comparing the treatment arm (standard of care + GEN-1) with the control arm (standard of care alone).

“During the first half of 2020, we reported data from the Phase I portion of the OVATION 2 Study that showed successful tumor resections, with seven out of eight patients (87.5%) in the GEN-1 treatment arm having a complete tumor resection (R0), which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. The NACT-only treatment arm had an R0 resection rate of 50%,” said Dr. Nicolas Borys, Celsion’s Chief Medical Officer. “The Company engaged Medidata/Acorn to independently evaluate our data using a propensity matched synthetic control arm (SCA) with results from the Company’s previously completed Phase I studies. The results suggested that GEN-1 nearly doubled progression-free survival (PFS) in these patients. These findings are not statistically significant, however, due to the small number of patients, but nonetheless are encouraging and supportive of our current Phase II study.”

“This past May we reported that the Data Safety Monitoring Board recommended that the Phase II portion of the OVATION 2 Study proceed with a GEN-1 dose of 100 mg/m2,” said Michael H. Tardugno, Chairman, President and Chief Executive Officer of Celsion. “Patients will undergo up to 6 months of immunostimulatory GEN-1 treatment. Based on results from earlier studies, we believe this regimen holds great potential to alter the current treatment paradigm, and in doing so improve survival for ovarian cancer patients, whose prognosis is generally poor. Our investigators are among the leading researchers in ovarian cancer. Together, we are delighted to have begun enrolling patients in the Study and look to achieve our goal of providing new novel therapeutic options to patients with this difficult-to-treat cancer.”

In March 2020 the Company announced the European Medicines Agency Committee for Orphan Medicinal Products recommended that GEN-1 be designated as an orphan medicinal product for the treatment of ovarian cancer. GEN-1 previously received orphan designation from the U.S. Food and Drug Administration for the treatment of ovarian cancer. This designation by the EMA provides 10 years of exclusivity once approved for marketing.

GEN-1, designed using Celsion's proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.