TSRA-196 Gets FDA Fast Track, Orphan Drug Designations for AATD

The US Food and Drug Administration has granted Fast Track and Orphan Drug designations to TSRA-196, an in vivo gene editing program from Tessera Therapeutics, for the treatment of adults with alpha-1 antitrypsin deficiency (AATD) who are homozygous for the PiZ allele (PiZZ).1

As described in a February 23, 2026, press release from the Company, TSRA-196 is being jointly developed with Regeneron and is designed to precisely correct the genetic mutation underlying AATD, with the goal of restoring production of functional alpha-1 antitrypsin (AAT) protein through a one-time, durable treatment option for patients.1

“Despite a clear understanding of the mutation that drives severe AATD, options are limited to life-long treatments that fail to address the underlying cause of the disease,” said David Davidson, MD, Chief Development and Medical Officer of Tessera Therapeutics.1 “Based on compelling evidence to date, we believe that TSRA-196 has the potential to permanently correct the underlying mutation responsible for this debilitating disease and address a high unmet need for a durable therapy. Fast Track and Orphan designations allow us to accelerate the development of TSRA-196 to dramatically improve the lives of people living with AATD, and we look forward to translating this promising mechanism into meaningful outcomes in our ongoing global first-in-human trial.”

In January, the FDA cleared Tessera’s Investigational New Drug (IND) application for TSRA-196 in AATD. The Company also received Australian Human Research Ethics Committee (HREC) approval to begin the phase 1/2 clinical trial to assess the safety, tolerability, and efficacy of TSRA-196 in adults with AATD.1,2

The first-in-human, open-label, multi-national study will administer a single intravenous administration of TSRA-196 and follow participants longitudinally for safety and key biomarkers relevant to AAT expression and function.1,2

Previous preclinical data presented at the American Society of Gene & Cell Therapy 28th Annual Meeting highlighted durable, high-fidelity genome editing of SERPINA1, the locus responsible for AATD, in mice and non-human primates following a single dose of TSRA-196, with high liver editing specificity, no germline or off-target editing, and favorable safety and tolerability using Tessera’s proprietary lipid nanoparticle delivery vehicle. These findings reinforce TSRA-196’s potential to correct the underlying genetic cause of AATD and support its advancement into clinical development.3

Despite not yet having any FDA-approved treatments, the therapeutic landscape for AATD is greatly expanding. In addition to TSRA-196’s Fast Track and Orphan Drug designations, YOLT-202, an investigational in vivo base editing therapy from YolTech Therapeutics, recently showed positive safety and tolerability as well as meaningful increases in AAT levels in evaluated patients treated with the 35 mg and 45 mg dose levels in an investigator-initiated trial.4

References

1. Tessera Therapeutics. Tessera Therapeutics Receives U.S. FDA Fast Track and Orphan Drug Designations for its Lead In Vivo Gene Editing Program TSRA-196 for the Treatment of Adults with AATD. February 23, 2026. Accessed February 23, 2026. https://www.tesseratherapeutics.com/news/tessera-therapeutics-receives-u-s-fda-fast-track-and-orphan-drug-designations-for-its-lead-in-vivo-gene-editing-program-tsra-196-for-the-treatment-of-adults-with-aatd

2. Tessera Therapeutics. Tessera Therapeutics Announces FDA Clearance of IND Application for its Lead In Vivo Gene Editing Program TSRA-196 for AATD. January 12, 2026. Accessed February 23, 2026. https://www.tesseratherapeutics.com/news/tessera-therapeutics-announces-fda-clearance-of-ind-application-for-its-lead-in-vivo-gene-editing-program-tsra-196-for-aatd

3. Tessera Therapeutics. Regeneron and Tessera Therapeutics to Jointly Develop TSRA-196, an Investigational Gene Editing Therapy for Alpha-1 Antitrypsin Deficiency (AATD). December 1, 2025. Accessed February 23, 2026. https://www.tesseratherapeutics.com/news/regeneron-and-tessera-therapeutics-to-jointly-develop-tsra-196-an-investigational-gene-editing-therapy-for-alpha-1-antitrypsin-deficiency-aatd

4. Brooks A. Single Dose YOLT-202 Gene-Editing Therapy Increases Functional AAT Levels in AATD. HCPLive. February 19, 2026. Accessed February 23, 2026. https://www.hcplive.com/view/single-dose-yolt-202-gene-editing-therapy-increases-functional-aat-levels-in-aatd