In-Licensing of DNase Technology Provides Opportunity to Address Multiple Oncology Indications

Adoptive transfer of CAR T cells has emerged as one of the most promising advances in cancer immunotherapy. Engineered CAR T cells, designed to recognize cancer-associated antigens, are capable of sustained and selective killing of tumor cells, with substantial reduction of tumor burden. CAR T therapies have exhibited remarkable clinical success against hematological malignancies but thus far have failed to demonstrate success in the context of solid tumors. Published evidence suggests that in addition to immunosuppressive factors, mechanical barriers formed by NETs can impede T-cell penetration and occlude T-cell contact with tumor cells.

Significant Unmet Need in Pancreatic Cancer

• 5‑year survival for advanced stage patients: ~3%¹
• Early detection is currently not feasible – most patients are at advanced stages

We plan to advance toward a first-in-human, multicenter, dose escalation and dose-expansion study of IV rhDNase I in subjects with locally advanced or metastatic solid tumors. Our systemic DNase program is initially targeting multi-billion-dollar indications including pancreatic carcinoma.

1: NIH National Cancer Institute, Surveillance, Epidemiology and End Results Program,Cancer Stat Facts: Pancreatic Cancer, https://seer.cancer.gov/statfacts/html/pancreas.html

Systemic DNase Treatment Improves Efficacy of PD-1 Blockade in Preclinical Tumor Models

Zhang, H.; Wang, Y.; Onuma, A.; He, J.; Wang, H.; Xia, Y.; Lal, R.; Cheng, X.; Kasumova, G.; Hu, Z.; Deng, M.; Beane, J.D.; Kim, A.C.; Huang, H.; Tsung, A. Neutrophils Extracellular Traps Inhibition Improves PD-1 Blockade Immunotherapy in Colorectal Cancer. Cancers 2021, 13, 5333. https://doi.org/10.3390/cancers13215333

 

DNase Armored CAR T: Proof of Concept

HER2-targeting, DNase-armored CAR T cells: