CRISPR Therapies for Alpha-1 Antitrypsin Deficiency Advance with New Data and FDA Designations
CRISPR therapies for alpha-1 antitrypsin deficiency advanced: BEAM-302 posted positive Phase 1/2 data, TSRA-196 gained FDA fast track/orphan status, and YOLT-202 raised AAT above the protective threshold.
Three CRISPR-based gene editing programmes for alpha-1 antitrypsin deficiency have advanced, with new clinical data and regulatory designations. Beam Therapeutics reports that its CRISPR-Cas-derived base editing candidate BEAM-302 corrects the SERPINA1 PiZ mutation in vivo, restoring functional AAT production. In Phase 1/2 data (n=29), a single 60 mg dose produced durable AAT increases (~16 µM), an ~84% reduction in toxic Z-AAT, and ~94% corrected M-AAT, with a favourable safety profile, supporting advancement to pivotal trials and potential accelerated approval.
Tessera Therapeutics’ CRISPR-Cas-based in vivo gene editing candidate TSRA-196 has received Fast Track and Orphan Drug designations from the FDA for treating PiZZ alpha-1 antitrypsin deficiency. Developed with Regeneron, TSRA-196 aims to precisely correct the causative mutation through a single intravenous dose, restoring functional AAT production. A Phase 1/2 trial is ongoing.
YolTech Therapeutics reports interim data showing that its CRISPR-Cas adenine base editor, YOLT-202, increased circulating alpha-1 antitrypsin in PiZZ patients with alpha-1 antitrypsin deficiency. In a first-in-human dose-escalation study, single intravenous doses (35 mg, 45 mg) produced rapid, dose-dependent rises above the 11 μM protective threshold, reaching normal levels at 45 mg, with >95% corrected M-AAT. Treatment was well tolerated, supporting planned IND submission.