Regeneron Pharmaceuticals is committing $150 million to begin an alliance on a Tessera Therapeutics gene-editing medicine nearing the clinic as a potential treatment for a rare disease that leads to debilitating effects on the liver and lungs.
The deal announced Monday puts Regeneron in the mix of a small group of companies working to bring patients genetic medicines that address the underlying cause of this disorder, alpha-1 antitrypsin deficiency, or AATD. For Tessera, a startup founded by Flagship Pioneering, the deal lends validation to both the therapy, TSRA-196, and the platform technology that produced it. The deal also provides that program with the financial resources to support its clinical development.
In AATD, a genetic mutation leads to abnormal alpha-1 antitrypsin (AAT), a liver-secreted protein that circulates throughout the body and protects lung tissue from certain enzymes. The misfolded versions of this protein accumulate in the liver leading to inflammation and fibrosis in that organ. The lack of AAT in circulation also leaves the lungs vulnerable to damage.
The standard treatment for AATD is augmentation therapy: regular infusions of AAT protein sourced from healthy donors. But such therapies only help with the lung damage from AATD and they don’t address the underlying cause of the disease, which stems from a mutation to SERPINA1, the gene that codes for AAT.
Tessera’s approach to genetic medicines comes from its “gene writing” platform, which it says writes therapeutic messages 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 whole genes with a one-time treatment.
In results from monkey tests reported earlier this year during the annual meeting of the American Society of Gene and Cell Therapy, Tessera said its experimental AATD treatment was well tolerated and showed “robust levels” of in vivo genome editing. The therapy also showed high specificity to the liver with no off-target activity detected.
The $150 million Regeneron has committed to begin the Tessera alliance includes both an upfront payment and an equity investment. Under the agreement, the two companies will share equally in global development costs and profits from sales of the therapy if it reaches the market. Tessera could also receive milestone payments reaching up to $125 million. Tessera will continue to oversee TSRA-196 through Phase 1 clinical development while Regeneron will take over responsibility for further clinical testing and potential commercialization. Tessera said it expects to file an investigational new drug application for TSRA-196 with the FDA by the end of this year.
“At Regeneron, we are strong believers in the power of genetics and genetic medicines to transform patients’ lives, and we have a robust portfolio of potential treatments to do just this,” George Yancopoulos, Regeneron board co-chair, 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 for Tessera’s gene editing approach.
There are efforts to improve on the approach of currently available AATD augmentation therapies. Sanofi’s efdoralpin alfa is an engineered version of AAT that comes from from the pharma giant’s $1.7 billion Inhibrx acquisition last year. In October, Sanofi reported Phase 2 results showing statistically significant increases in functional AAT protein. Other experimental approaches for treating AATD include RNA-editing medicines. GSK-partnered Wave Life Sciences and Korro Bio lead this camp, but both have reported lower than expected levels of AAT protein from early clinical results posted in recent months. Startup AIRNA raised $155 million earlier this year as it prepares to advance its RNA-editing AATD therapy to the clinic.
The RNA-editing therapies require dosing at regular intervals. The genetic medicine closest to Tessera’s approach is Beam Therapeutics’ BEAM-302, which uses base-editing to fix the SERPINA1 genetic 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 BEAM-302 led to increases in functional AAT protein.
The Tessera partnership broadens Regeneron’s scope in genetic medicines. The company has a longstanding 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 experimental treatment for hereditary transthyretin amyloidosis, a rare protein misfolding disorder affecting the liver and the heart. The FDA placed this gene-editing therapy’s Phase 3 tests under a clinical hold after liver complications emerged in the cardiomyopathy study. That patient later died.
The Regeneron pipeline also has DB-OTO for an inherited form of hearing loss. This gene therapy came from Regeneron’s 2023 Decibel Therapeutics acquisition. In October, Regeneron presented Phase 1/2 data showing DB-OTO led to clinically meaningful hearing improvement in 10 of 11 children who received the one-time treatment. At the time of the announcement, Regeneron said it planned to submit an application by the end of the year seeking FDA approval for DB-OTO.
Photo: Michael Nagle/Bloomberg, via Getty Images
