Regeneron invests $150 million to partner with gene-edited treatment Tessera for rare liver and lung disorders

Regeneron Pharmaceuticals is committing $150 million to launch an alliance on a gene-editing drug from Tessera Therapeutics close to the clinic as a potential treatment for a rare disease that causes debilitating effects on the liver and lungs.

The deal announced Monday places Regeneron among a small group of companies working to bring patients genetic medicines that address the underlying cause of the disorder, alpha-1 antitrypsin deficiency, or AATD. For Tessera, a startup founded by Flagship Pioneering, the deal validates both the therapy, TSRA-196, and the technology platform that produced it. The agreement also provides this program with the financial resources necessary to support its clinical development.

In AATD, a genetic mutation leads to abnormal alpha-1 antitrypsin (AAT), a protein secreted by the liver that circulates throughout the body and protects lung tissue from certain enzymes. Misfolded versions of this protein accumulate in the liver, leading to inflammation and fibrosis in this organ. The lack of circulating AAT also makes the lungs vulnerable to damage.

The standard treatment for AATD is augmentation therapy: regular infusions of AAT protein from healthy donors. But such therapies only alleviate the lung damage caused by AATD and do not address the underlying cause of the disease, which comes from a mutation in SERPINA1, the gene that encodes AAT.

Tessera’s approach to genetic medicine comes from its “gene writing” platform, which it says writes therapeutic messages into the genome by modifying one or more DNA base pairs. These lipid nanoparticle-delivered therapies can precisely correct insertions or deletions, or add exon-length sequences and entire genes with a single treatment.

In monkey test results reported earlier this year at the annual meeting of the American Society for Gene and Cellular Therapy, Tessera said its experimental AATD treatment was well tolerated and showed “robust levels” of genome editing in vivo. The therapy also showed high specificity for the liver, with no off-target activity detected.

The $150 million Regeneron committed to launch the Tessera Alliance includes both an upfront payment and an equity investment. Under the terms of the agreement, the two companies will equally share global development costs and profits from sales of the therapy if it comes to market. Tessera could also receive milestone payments of up to $125 million. Tessera will continue to oversee TSRA-196 through Phase 1 clinical development, while Regeneron will assume responsibility for continued clinical testing and potential commercialization. Tessera said it plans to file an investigational new drug application for TSRA-196 with the FDA by the end of this year.

“At Regeneron, we strongly believe in the power of genetics and genetic medicines to transform patients’ lives, and we have a strong pipeline of potential treatments to do just that,” George Yancopoulos, Regeneron’s co-chairman, president and chief scientific officer, said in a prepared statement. “Alpha-1 antitrypsin deficiency is a serious disease with limited treatment options today and is particularly well suited to Tessera’s gene editing approach.

Efforts are being made to improve the approach to currently available AATD augmentation therapies. Sanofi’s efdoralpine alfa is a technical version of AAT that emerged from the pharmaceutical giant’s $1.7 billion acquisition of Inhibrx last year. In October, Sanofi released phase 2 results showing statistically significant increases in functional AAT protein. Other experimental approaches to treating AATD include RNA-editing drugs. GSK partners Wave Life Sciences and Korro Bio are leading this camp, but both reported lower-than-expected levels of AAT protein based on initial clinical results published in recent months. Startup AIRNA raised $155 million earlier this year as it prepares to advance its RNA-editing therapy AATD into the clinic.

RNA editing therapies require dosing at regular intervals. The closest genetic medicine to Tessera’s approach is Beam Therapeutics’ BEAM-302, which uses base editing to correct the disease-causing SERPINA1 genetic mutation. Like Tessera’s AATD therapy, BEAM-302 is an in vivo single editing therapy. Earlier this year, Beam reported encouraging phase 1 data showing that BEAM-302 led to an increase in functional AAT protein.

The Tessera partnership expands Regeneron’s reach in the field of genetic medicines. The company has a long-standing alliance with Intellia Therapeutics focused on the development of CRISPR-based in vivo gene editing therapies for neurological and muscular diseases. One of the programs covered by this partnership is nex-z, an investigational treatment for hereditary transthyretin amyloidosis, a rare protein misfolding disorder affecting the liver and heart. The FDA placed phase 3 testing of this gene-editing therapy on clinical hold after liver complications emerged in the cardiomyopathy study. This patient later died.

The Regeneron pipeline also has DB-OTO for an inherited form of hearing loss. This gene therapy emerged from Regeneron’s acquisition of Decibel Therapeutics in 2023. In October, Regeneron presented phase 1/2 data showing that DB-OTO resulted in clinically significant hearing improvement in 10 of 11 children who received the single treatment. At the time of the announcement, Regeneron said it planned to submit an application by the end of the year to obtain FDA approval for DB-OTO.

Photo: Michael Nagle/Bloomberg, via Getty Images