Intellia Therapeutics, Poseida Therapeutics, YolTech Therapeutics, and KSQ Therapeutics have recently announced significant updates regarding their gene-editing clinical trials, marking advancements in the treatment of hereditary angioedema, multiple myeloma, primary hyperoxaluria type 1, and solid tumors, respectively. These developments highlight the expanding role of gene editing technologies in addressing previously unmet medical needs.
Intellia Therapeutics Advances NTLA-2002 for Hereditary Angioedema
Intellia Therapeutics has initiated a global, pivotal Phase 3 trial, named HAELO, to evaluate NTLA-2002 for the treatment of hereditary angioedema (HAE). HAE is a rare genetic disease characterized by severe inflammatory attacks. The HAELO trial will enroll 60 adults with Type I or Type II HAE, randomized 2:1 to receive a single intravenous infusion of NTLA-2002 or a placebo. NTLA-2002 is designed to knock out the KLKB1 gene, reducing plasma kallikrein activity and preventing HAE attacks. Long-term Phase 1 data demonstrated significant reductions in HAE attack rates and plasma kallikrein levels. The primary endpoint of the HAELO trial is the change in the number of HAE attacks from Week 5 through Week 28.
Poseida Therapeutics Shows Promise in Multiple Myeloma with P-BCMA-ALLO1
Poseida Therapeutics reported new interim clinical data from its ongoing Phase 1/1b trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM). The data revealed a 91% overall response rate (ORR) in heavily pre-treated patients who had received three or more prior lines of therapy. Specifically, a 100% ORR was observed in BCMA-naïve patients, and an 86% ORR in those who had received prior BCMA- and/or GPRC5D-targeting treatment. P-BCMA-ALLO1 is a fully allogeneic, T stem cell memory (TSCM)-rich CAR-T therapeutic candidate engineered to target the B cell maturation antigen (BCMA). The ongoing trial is being conducted in partnership with Roche.
YolTech Therapeutics Targets Primary Hyperoxaluria Type 1 with YOLT-203
YolTech Therapeutics has received Orphan Drug Designation from the FDA for YOLT-203, an in vivo gene-editing therapeutic candidate for primary hyperoxaluria type 1 (PH1). PH1 is an inherited metabolic disorder caused by mutations in the AGXT gene, leading to an accumulation of oxalate in the kidney and other organs. YOLT-203 aims to correct mutations in AGXT, reducing harmful oxalate levels. The early Phase 1 trial is evaluating the safety and tolerability of YOLT-203 in Chinese individuals with PH1, assessing the impact of a single dose on plasma oxalate levels. Pre-clinical studies demonstrated high gene-editing activity and in vivo editing efficiency.
KSQ Therapeutics Advances CRISPR-Edited TIL Therapy KSQ-004EX for Solid Tumors
KSQ Therapeutics announced that the FDA has cleared its IND application for KSQ-004EX, a CRISPR-Cas9 engineered tumor-infiltrating lymphocyte (TIL) therapeutic candidate. KSQ can now initiate a Phase 1/2 clinical trial of KSQ-004EX for patients with advanced solid tumors, including melanoma, head and neck squamous cell carcinoma, non-small-cell lung cancer, colorectal cancer, pancreatic cancer, and cervical cancer. KSQ-004EX consists of TIL in which Suppressor of cytokine signaling 1 (SOCS1) and Regnase-1 are inactivated using CRISPR-Cas9 gene editing. These targets were identified as key regulators of anti-tumor potency and persistence of TIL in pre-clinical models.
