KSQ Therapeutics' CRISPR-Engineered TIL Therapy, KSQ-004EX, Receives FDA IND Clearance for Advanced Solid Tumors
Key Insights
KSQ Therapeutics (search) received FDA clearance for its IND application for KSQ-004EX, a CRISPR/Cas9-engineered tumor-infiltrating lymphocyte (TIL) therapy.
KSQ-004EX targets advanced solid tumors (search) by inactivating SOCS1 (search) and Regnase-1 (search) genes in TILs, enhancing anti-tumor potency and persistence.
A Phase 1/2 open-label, dose-escalation study will assess the safety, tolerability, and anti-tumor activity of KSQ-004EX in select advanced solid tumors (search).
KSQ Therapeutics (search), in collaboration with The University of Texas MD Anderson Cancer Center and the Cell Therapy Manufacturing Center (CTMC), has announced that the FDA has cleared the Investigational New Drug (IND) application for KSQ-004EX, its second engineered tumor-infiltrating lymphocyte (eTIL®) program, moving the novel cell therapy into a Phase 1/2 clinical trial for advanced solid tumors (search). KSQ-004EX is engineered using CRISPR/Cas9 gene editing to inactivate the genes encoding SOCS1 (search) and Regnase-1 (search) within TILs.
Targeting Solid Tumors with Enhanced TIL Therapy
KSQ's CRISPRomics® platform identified SOCS1 (search) and Regnase-1 (search) as key regulators of anti-tumor potency and persistence of TILs. Preclinical models suggest that KSQ-004EX has best-in-class potential for treating advanced solid tumor indications. The therapy is manufactured by CTMC using KSQ’s ExPRESS™ process, utilizing patient tumor samples, including core biopsies, as the starting material.
Clinical Trial Design and Objectives
The Phase 1/2 clinical trial is designed as an open-label, dose-escalation study. It will enroll patients with select advanced solid tumors (search). The primary objective of the Phase 1 portion is to evaluate the safety and tolerability of KSQ-004EX. The primary objective of Phase 2 is to evaluate anti-tumor activity in multiple indication-specific cohorts.
Preclinical Promise
Preclinical studies have demonstrated that KSQ-004EX exhibits enhanced anti-tumor function in solid tumor models that are refractory to PD-1 (search) inhibition, suggesting a potential breakthrough in treating cancers that are resistant to current immunotherapies.
Expert Commentary
"As we continue to learn more about the biology of our eTIL candidates, we gain confidence that they can redefine the treatment of solid tumors (search), including difficult-to-treat cancers. We’re excited to bring an additional therapy into the clinic with the experts at MD Anderson, where this study will be initiated," said Qasim Rizvi, Chief Executive Officer of KSQ.
Rodabe Amaria, M.D., professor of Melanoma (search) Medical Oncology at MD Anderson and principal investigator of the KSQ-004EX study, added, "Solid tumor treatment continues to be a significant challenge in oncology. The ability to offer patients a novel cell therapy is encouraging. The preclinical KSQ-004EX data is promising, and we look forward to exploring the potential of KSQ’s dual-edited TIL."