NEW YORK, NY /  May 14, 2020 / CLS Therapeutics, a preclinical-stage anticancer gene therapy platform company developing novel medicines to bring the curative power of cell-free DNA destruction to patients with tumors, presented preclinical data on its AAV therapy clinical candidate, CLS-014, this week at the annual meeting of the American Society of Gene and Cell Therapy (ASGCT).

Abstract Title (Poster 1178): First-In-Class AAV-Based Gene Therapy for Pancreatic Cancer and Other Tumors Based on the Destruction of Cell-Free DNA with Vector-Delivered DNase I

Session: Cancer – Targeted Gene and Cell Therapy

Date/Time: Thursday May 14, 2020 5:30 PM – 6:30 PM

Speaker: George Tetz, M.D., Ph.D., CEO of CLS-Therapeutics, Inc

CLS-Therapeutics is developing CLS-014 as a novel standard of care in a broad range of cancers, including pancreatic cancer, colorectal cancer and other. CLS-014, is AAV-mediated Deoxyribonuclease I (DNase I) liver gene therapy.DNase I, an inhibitor of NETs, has been shown to alter NET function by cleaving the DNA strands comprising the NET backbone. DNase I displays high anti-metastatic activity in multiple tumor models. While effective in preclinical animal model studies, this intervention requires long term daily parenteral administrations. In order to circumvent this and certain other limitations and to provide a more translationally applicable treatment, we have developed an AAV gene therapy vector to specifically express DNase I in the liver and evaluated its therapeutic potential in a mouse model of pancreatic cancer. In this study, we demonstrate that AAV mediated DNase I liver gene transfer following a single intravenous injection demonstrated a significant decrease in tumor bioluminescence (by more than 53%) compared to untreated control (p < 0.05). The number of ovary, kidney, spleen, and liver metastatic cells were significantly lower in the group treated with Nab-paclitaxel + CLS-014 than in both the untreated control group and the group treated only with Nab-paclitaxel (p<0.05). CLS-014 enabled a significant increase in serum DNase I levels compared to untreated controls.

Conclusion: This study shows a potential in the cancer therapeutic strategy employing a gene-therapy approach allowing long-term expression of DNase I and destruction of NETs and tumor derived cfDNA.