Regeneron invests $150 million in Tessera gene-editing drug partnership to treat rare liver and lung diseases
Regeneron Pharmaceuticals has committed $150 million to launch Tessera Therapeutics, a gene-editing drug alliance that is about to enter clinical stages as a potential treatment for a rare disease that causes weakening of the liver and lungs.
The deal, announced Monday, joins Regeneron among a small group of companies working to bring genetic medicines to patients that address the underlying cause of the disease, alpha-1 antitrypsin deficiency (AATD). For Tessera, a startup founded by Flagship Pioneering, the deal validates the TSRA-196 therapy and the platform technology to produce it. The deal also provides the program with financial resources to support its clinical development.
In AATD, genetic mutations cause abnormalities in 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, causing inflammation and fibrosis in the organ. A lack of circulating AAT also makes the lungs susceptible to damage.
The standard treatment for AATD is augmentation therapy: regular infusions of AAT protein from healthy donors. But such treatments can only help alleviate the lung damage caused by AATD and do not address the underlying cause of the disease, which stems from mutations in SERPINA1, the gene that codes for AAT.
Tessera's genetic medicine approach comes from its “gene writing” platform, which writes therapeutic information into the genome by changing single or multiple DNA base pairs. These lipid nanoparticle-delivered therapies can precisely correct insertions or deletions, or add exon-length sequences and entire genes in a single treatment.
In monkey test results presented earlier this year at the American Society of Gene and Cell Therapy's annual meeting, 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.
Regeneron has committed $150 million to launch the Tessera Alliance, which includes an upfront payment and an equity investment. Under the agreement, the two companies will share equally the global development costs and sales profits of the treatment if it reaches the market. Tessera can also receive up to $125 million in milestone payments. Tessera will continue to oversee the Phase 1 clinical development of TSRA-196, while Regeneron will be responsible for further clinical testing and potential commercialization. Tessera said it expects to submit an investigational new drug application for TSRA-196 to the FDA before the end of this year.
“At Regeneron, we believe strongly in the power of genetics and genetic medicines to transform patients' lives, and we have a powerful portfolio of potential treatments to achieve this goal,” George Yancopoulos, co-chairman of Regeneron's board of directors, president and chief scientific officer, said in a prepared statement. “Alpha-1 antitrypsin deficiency is a serious disease with limited current treatment options and is particularly well suited for Tessera's gene editing approach.
Efforts are ongoing to improve currently available methods of enhancing AATD therapy. Sanofi's efdoralpin alfa is an engineered version of AAT from Inhibrx, which the pharmaceutical giant acquired last year for $1.7 billion. In October, Sanofi reported Phase 2 results showing a statistically significant increase in functional AAT protein. Other experimental approaches to treating AATD include RNA-editing drugs. GlaxoSmithKline's (GSK) collaboration Wave Life Sciences and Korro Bio are leading the way in this camp, but both companies reported lower than expected AAT protein levels based on early clinical results released in recent months. Startup AIRNA raised $155 million earlier this year as it prepares to advance its RNA-editing AATD therapy into the clinic.
RNA-editing therapies require regular dosing. The genetic drug closest to Tessera's approach is Beam Therapeutics' BEAM-302, which uses base editing to repair the SERPINA1 gene mutation at the root of the disease. Like Tessera's AATD therapy, BEAM-302 is a one-time in vivo editing therapy. Earlier this year, Beam reported encouraging Phase 1 data showing that BEAM-302 resulted in an increase in functional AAT protein.
The Tessera partnership expands Regeneron's reach in the genetic medicine space. The company has a long-term alliance with Intellia Therapeutics focused on developing CRISPR-based in vivo gene editing therapies for neurological and muscle diseases. One of the programs covered by the collaboration is nex-z, an experimental treatment for hereditary transthyretin amyloidosis, a rare protein misfolding disease that affects the liver and heart. The FDA has paused a Phase 3 trial of this gene-editing therapy after liver complications emerged in a cardiomyopathy study. The patient later died.
The Regeneron pipeline also features DB-OTO for hereditary hearing loss. The gene therapy comes from Decibel Therapeutics, which Regeneron acquired in 2023. In October, Regeneron announced Phase 1/2 data showing that DB-OTO produced clinically meaningful hearing improvements in 10 of 11 children who received the one-time treatment. In announcing the news, Regeneron said it plans to submit an application to seek FDA approval of DB-OTO before the end of this year.
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