Regeneron and Tessera advance TSRA-196 toward IND/CTA filings

“Tessera is on the cusp of a critical inflection point as we prepare to enter the clinic in the near term. We are excited to partner with Regeneron, a global leader in innovative biotechnology and genetic medicine, to accelerate the development of TSRA-196 and broaden its potential impact to patients in need”Michael Severino, CEO of Tessera Therapeutics

In non-human primates, a single 1.5 mg/kg dose of Tessera’s RNA Gene Writer targeting SERPINA1 achieved robust genome editing, with an estimated 76% hepatocyte editing at the disease locus. Editing exhibited high fidelity, with a 195:1 ratio of intended to unintended edits at the target site. Specificity studies across 30 tissues showed that editing was primarily confined to the liver; only the spleen exhibited measurable editing above background (0.14%), and no editing was detected in germline tissues. Importantly, no off-target editing was identified at other genomic loci.

Durability was also demonstrated in NHPs. Animals with 80% hepatocyte editing maintained stable correction for at least six months, confirmed by both genomic DNA and mRNA analyses. In the PiZ mouse model of AATD, the RNA Gene Writer achieved therapeutically relevant correction at very low doses, including 70% genomic correction at 0.05 mg/kg and 95% at 0.5 mg/kg, corresponding to 92% and 100% restoration of serum AAT to wild-type levels, respectively.

Treated animals showed durable phenotypic rescue, including a 75% reduction in hepatic AAT aggregates and restoration of normal liver histology 10 weeks post-treatment. Tessera’s proprietary LNP delivery system demonstrated favourable tolerability in NHPs, with no clinically meaningful elevations in liver enzymes or signs of coagulopathy at doses up to 2 mg/kg.

Together, these data underscore the potential of TSRA-196 to provide a one-time, durable correction of SERPINA1 mutations. Under the collaboration, Tessera will lead early clinical development, while Regeneron assumes responsibility for global development and commercialisation. The companies will share costs and profits equally, with Tessera receiving $150 million upfront and eligibility for an additional $125 million in near-term milestones.

If TSRA-196 clears IND/CTA review, it will advance as the first clinical program built on Tessera’s Gene Writing platform – a technology aiming to rewrite endogenous DNA sequences without double-strand breaks, offering a fundamentally new approach to treating monogenic liver diseases.

For more information read the press release.