PIPELINE

Harnessing the building blocks of life to work in harmony with the body’s immune system

GEN-1

GEN-1, an IL-12 DNA plasmid vector formed into nanoparticles with a lipopolymeric delivery system, is the first product designed via the TheraPlas platform technology. TheraPlas has proven to be an effective immunotherapy for treating various types of tumors when utilized in combination with an interleukin-12 (IL-12) plasmid. IL-12 is one of the most active cytokines for stimulating an immune response against cancer.

IL-12: A Powerful Immune-Modulating Agent

TheraPlas™ is a technology platform that can deliver nucleic acid-based therapeutics via novel synthetic delivery systems that are independent of viral vectors or devices. Capable of providing cell transfection with double-stranded DNA plasmids as well as large therapeutic RNA segments, it represents a novel approach to improving the safety and efficacy of gene-based therapies.

GEN-1 circumvents toxicity issues typically associated with IL-12

IL-12, when administered as a recombinant protein, requires frequent and large bolus administration. This results in significant toxicity. GEN-1 addresses the toxicity issues associated with IL-12. Its nanoparticle profile enables cell transfection followed by persistent, local secretion of IL-12 at therapeutic levels for several days, while avoiding the toxicities associated with recombinant IL-12. Targeted administration directly to the tumor location also helps reduce toxicities because very little IL-12, if any, enters the systemic circulation.

✓ Local administration to improve targeting
✓ Stimulates the body’s immune system to attack cancer
✓ Plasmid vehicle avoids pitfalls of viral vector
✓ Provides persistent increases in IL-12 levels in tumor microenvironment

Strong safety profile and encouraging clinical results in ovarian cancer patients

Biological activity, safety and clinical benefits have been demonstrated in platinum-resistant/sensitive and newly diagnosed ovarian cancer in multiple clinical studies where GEN-1 was administered as a single agent or as a combination agent with chemotherapy. Over 100 patients have been safely treated with GEN-1 and the highest safe dose from monotherapy and combination therapy studies examined to date has been 100 mg/m2. Preclinical and clinical studies suggest that GEN-1 can be safely and repeatedly administered for the treatment of a variety of tumor types including ovarian, colorectal, and bladder cancers.

Evidence of biological activity

Survival rates by dose

Clinical studies using GEN-1

OVATION 2 Study This phase I/II randomized, open label trial is currently in Phase II in newly diagnosed patients. The primary objective of the study is to evaluate safety and compare progression free survival between neoadjuvant chemotherapy (NACT) plus GEN-1 versus standard NACT. This is a randomized, open label, multicenter trial in which eligible subjects will be assigned 1:1 to the treatment and control arms. The Phase I portion of the study determined the dosing for the Phase II portion to be safe at 100 mg/m2 and is also evaluating efficacy and biological activity.

OVATION Study This Phase I trial in newly diagnosed patients with advanced ovarian cancer was conducted to determine safety and the maximum tolerated dose of GEN-1 as part of a neoadjuvant therapy to first-line standard of care, followed by surgery. The study also evaluated dose-related biological response to IL-12 along with other clinical endpoints. The results of the study have been published in the journal Clinical Cancer Research.

Disease applications for GEN-1

Ovarian cancer is the most lethal of gynecological malignancies among women, with an overall 5-year survival rate of 49%. There are approximately 21,500 new cases of ovarian cancer expected in the United States in 2021 with an estimated 14,000 deaths (Cancer Stat Facts: Ovarian Cancer; SEER.cancer.gov, accessed 11-Oct-2021). Mortality rates for ovarian cancer declined very little in the last 40 years, due to lack of early detection tests and little improvement in treatments.

Peritoneal cavity cancers including colorectal, pancreatic, uterine, bladder, and stomach cancers, among others are future targets for GEN-1 research. Administered in the peritoneal cavity, GEN-1’s promise to change the local tumor micro-environment to “pro-immune/anticancer” has the potential to change the course of treatment for these deadly malignancies.