May 17, 2025

Tessera Therapeutics Presented new preclinical data in non-human primates (NHP) for alpha-1 antitrypsin deficiency (AATD) and phenylketonuria (PKU), where RNA Gene Writer achieved an estimated 76% and 70% editing in hepatocytes1, respectively New AATD data reinforced the safety and precision of Tessera’s proprietary LNP delivery system, demonstrating that it was well tolerated in NHP with high liver specificity and no off-target activity detected Preclinical data for sickle cell disease (SCD) across mouse and NHP models highlight Tessera’s RNA Gene Writers’ ability to drive durable and efficient gene editing greater than 20% in long-term hematopoietic stem cells (LT-HSCs), reaching a potentially curative threshold SOMERVILLE, Mass., May 17, 2025 (GLOBE NEWSWIRE) -- Tessera Therapeutics, the biotechnology company pioneering a new approach in genetic medicine known as Gene Writing™, is presenting updates across its in vivo genetic medicine programs for AATD, PKU, and SCD, as well as advances in in vivo T cell therapies. These data were shared across four oral presentations and three poster presentations at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place in New Orleans, Louisiana, May 13 – 17, 2025. “The ability to achieve durable, highly efficient gene editing in vivo – including in the liver, hematopoietic stem cells, and T cells – positions Tessera to address multiple disease areas,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “As we move closer to the clinic, these results underscore the potential of our Gene Writing and delivery platforms to advance a new class of genetic medicines that could one day transform the treatment of AATD, PKU, and SCD, and oncologic and autoimmune diseases.” In Vivo AATD Data AATD is a monogenic disease of the liver caused by mutations in the SERPINA1 gene, resulting in an abnormal form of the alpha-1 antitrypsin (AAT) protein that causes both lung and liver manifestations. Preclinical data in NHPs following a single dose of 1.5 mg/kg of RNA Gene Writer formulated with a proprietary LNP delivery vehicle, continued to show robust levels of genome editing, achieving an estimated 76% in hepatocytes1 at the SERPINA1 locus. High fidelity was observed with a 195 to 1 ratio of intended to unintended edits at the target locus. As part of Tessera’s evaluation of the genomic safety profile of its RNA Gene Writer, NHP data displayed high specificity of editing to the liver with only spleen showing quantifiable levels of editing above background (0.14%) among 30 additional tissues tested. Importantly, editing was not detected in germline tissues, including testes and ovaries. Editing was also highly specific to the intended SERPINA1 locus, with no off-target activity detected at other genetic loci. In addition, a study in NHPs where 80% editing of hepatocytes was achieved by an RNA Gene Writer targeting SERPINA1 demonstrated this editing was durable for at least six months, as supported by genomic DNA analysis of whole liver samples and cDNA analysis of edited mRNA transcripts. Data were also presented from an RNA Gene Writer that achieved therapeutically relevant levels of correction at very low doses in the PiZ mouse model, including 70% genomic correction in hepatocytes at 0.05 mg/kg, and 95% at 0.5 mg/kg that corresponded to 92% and 100% correction of serum AAT protein to wild-type. Durable mutation correction and phenotypic rescue was observed including a 75% reduction of AAT aggregates by liver histology that resulted in less than 5% of liver area being occupied by toxic aggregates in the 0.5 mg/kg treated group at 10 weeks post-treatment. Further data featured on Tessera’s proprietary LNP delivery vehicle demonstrated that it was well tolerated in NHPs, with no clinically meaningful elevation in liver enzyme levels and no signs of coagulopathy at doses of 1 and 2 mg/kg. In Vivo PKU Data PKU is a monogenic disease of the liver caused by mutations in the phenylalanine hydroxylase (PAH) gene, which leads to the inability to metabolize the dietary amino acid phenylalanine (Phe), resulting in toxic Phe accumulation and neurocognitive impairment. Preclinical data in NHPs was presented from a single dose of RNA Gene Writer formulated with a proprietary LNP delivery vehicle, where an estimated 70% editing of the PAH locus was achieved in hepatocytes1 at 2 mg/kg, with supporting cDNA analysis demonstrating 67% of PAH mRNA was edited. Data was also presented from an RNA Gene Writer that achieved an estimated 65% correction in hepatocytes at 0.2 mg/kg in the humanized R408W mouse model, normalizing plasma Phe levels in a mouse disease model. In Vivo SCD Data SCD is the most common lethal monogenic disease globally, arising from a mutation in the hemoglobin beta-globin (HBB) gene that results in hemoglobin S, which can cause red blood cell sickling, acute and chronic pain, and widespread organ damage. Multiple proof-of-concept studies of Gene Writer formulated in a proprietary LNP delivery vehicle were presented, achieving greater than 20% HBB editing in LT-HSCs with repeat dose in two NHP species, including cynomolgus and rhesus, reaching potentially curative levels. Single cell analysis of HSCs collected from treated NHP showed ~35-50% of cells had at least one edited HBB gene. Edited cells demonstrated durability across multiple loci in NHP, out to 6 months with beta-2 microglobulin (B2M) surrogate editing and out to 4 months with HBB editing, with edited cells supporting long-term self-renewal and multi-lineage development. In a humanized mouse model engrafted with mobilized peripheral blood cells from individuals with SCD, RNA Gene Writer achieved approximately 35% in vivo correction of the HBB gene in LT-HSCs. Additional data in a humanized wild-type mouse model showed that RNA Gene Writer achieved greater than 50% HBB editing in LT-HSCs across multiple donors. These results across mouse and NHP models highlight Tessera’s Gene Writing and delivery platforms’ ability to drive efficient gene correction in clinically relevant cell populations, representing a significant advancement towards a potentially curative, durable and non-viral approach for treating SCD that will neither require stem cell mobilization/transplantation nor myeloablative pre-conditioning. Human mixed donor chimerism studies demonstrate that 20% chimerism can reverse the sickle phenotype in patients following allogeneic hematopoietic stem cell transplant.2 Advances Towards In Vivo T-Cell Therapies Tessera is applying its Gene Writing and proprietary LNP delivery platforms to develop in vivo cell therapies for potential oncology and autoimmune disease applications. Proof-of-concept mouse studies demonstrated that a single intravenous infusion of RNA Gene Writer, delivered in a proprietary LNP, successfully generated functional CAR-T cells in vivo targeting CD19 and CD20. In a tumor-bearing xenograft model, this approach led to CD19 CAR-T cell expansion and complete tumor clearance. In a naïve humanized mouse model, an average of 30% CD20-targeted CAR writing was achieved in resting T cells, resulting in the elimination of circulating human B cells. ___________________