Tarrytown, New York & Somerville, Massachusetts, December 1, 2025 — Regeneron and Tessera Therapeutics have announced a global collaboration to develop TSRA-196, an investigational in vivo gene-writing therapy designed to correct the genetic mutation underlying alpha-1 antitrypsin deficiency (AATD), potentially offering a one-time, durable treatment for patients afflicted by this severe genetic disorder. under the agreement, Tessera will receive an upfront investment from Regeneron and both companies will co-develop and commercialize the therapy worldwide. AATD is a monogenic disease caused by mutations in the SERPINA1 gene, leading to misfolded alpha-1 antitrypsin (AAT) protein that accumulates in the liver and leaves lung tissue vulnerable — resulting in progressive liver disease, lung disease (emphysema), or both. Current therapies are limited to symptomatic management and, in lung disease, repeated protein infusions. TSRA-196 aims to permanently correct the defective gene in the patient’s liver using Tessera’s proprietary Gene Writing™ platform and non-viral delivery technologies, thereby restoring functional AAT production from within the body. This approach could transform the treatment paradigm for AATD — shifting from life-long symptomatic treatment to a potential curative, single-dose therapy.
Science Significance
The scientific ambition behind TSRA-196 lies in the emerging field of gene writing — a next-generation genome engineering technology that goes beyond traditional gene editing. Instead of simply cutting and repairing DNA, gene writing enables precise insertion, correction, or rewriting of genetic sequences, potentially with greater fidelity and lower off-target risks. TSRA-196 leverages this capability to correct the SERPINA1 mutation at the DNA level, enabling hepatocytes (liver cells) to produce normal AAT protein. Preclinical data in non-human primates reportedly show durable, high-fidelity gene correction, high liver specificity and no detectable off-target or germline edits, alongside favourable tolerability. These findings suggest that gene writing may overcome longstanding challenges in in vivo genetic medicine — positioning TSRA-196 as a pioneer for safe, durable and systemically delivered genetic therapies.
Regulatory Significance
Under the collaboration agreement, the companies plan to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by the end of 2025, initiating the first-in-human clinical trial. This step is critical: regulatory agencies will scrutinize not only efficacy but also genome integrity, off-target risk, delivery vector safety, durability, and immunogenicity. Success at this stage could mark the first approval pathway for gene-writing therapies targeting a common monogenic disorder — setting regulatory precedents for the emerging class of in vivo genetic medicines. The project may also qualify for orphan-drug incentives, given AATD’s rare-disease status.
Business Significance
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Financially and strategically, the collaboration is significant: Tessera receives a substantial upfront investment, and both companies will share worldwide development costs and future profits. For Regeneron, known for genetic-medicine capabilities and clinical development infrastructure, this deal expands its portfolio into curative gene therapies — a high-growth, high-value frontier. For Tessera, it validates its Gene Writing platform with one of the industry’s leading biotech firms, offering resources, global reach, and commercialization clout. The partnership positions TSRA-196 as a potential template for future gene-writing collaborations in other monogenic diseases.
Patients’ Significance
For individuals with AATD — many of whom face progressive liver damage, cirrhosis, lung disease and reduced lifespan — TSRA-196 represents a potential once-and-done therapy that could correct the genetic defect at its source and restore healthy AAT production. This would eliminate the need for lifelong protein infusions, reduce disease complications, and significantly improve quality of life. If successful, the therapy could prevent liver transplants and long-term lung impairment, transforming outcomes for thousands of patients worldwide.
Policy Significance
The development of TSRA-196 aligns with broader health-policy objectives pushing for curative genetic medicines, especially for rare inherited diseases. Gene-writing treatments like TSRA-196 could help reduce long-term burden on healthcare systems by preventing chronic disease progression, hospitalizations, and transplantation costs. Additionally, establishing safe, effective in vivo gene-writing therapies may prompt regulators and payers to revisit reimbursement frameworks, orphan drug incentives, and access models — potentially shaping future global policies for genetic medicines.
The Regeneron–Tessera collaboration to develop TSRA-196 marks a landmark moment in genetic medicine — blending cutting-edge gene writing technology with clinical-scale drug development muscle to tackle alpha-1 antitrypsin deficiency at its root. With preclinical proof-of-concept in hand, a planned IND filing looming, and a structure in place for global development and commercialisation, TSRA-196 may set the standard for a new generation of curative one-time gene therapies. If successful, it could transform treatment paradigms not only for AATD but for a wide array of inherited diseases, offering hope for patients and reshaping the future of medicine.
Source: Regeneron press release
