Alltrna Announces Approval to Initiate First-in-Human Clinical Trial of AP003, the First tRNA Therapeutic to Enter Clinical Trials

• A Phase 1 healthy volunteer trial has been approved in Australia and will be initiated under the Australia Therapeutic Goods Administration (TGA) Clinical Trial Notification scheme
• This trial will evaluate the safety and pharmacokinetics of AP003, an engineered tRNA therapeutic in development to treat Stop Codon Disease caused by an arginine-to-TGA (Arg-TGA) premature termination codon

CAMBRIDGE, Mass., March 31, 2026 /PRNewswire/ -- Alltrna, a Flagship Pioneering company unlocking transfer RNA (tRNA) biology and pioneering tRNA therapeutics to regulate the protein universe and resolve disease, today announced approval to initiate a Phase 1 clinical trial of AP003 in healthy volunteers in Australia. The study has been approved under Australia's Therapeutic Goods Administration (TGA) Clinical Trial Notification (CTN) scheme, following review by the Human Research Ethics Committee (HREC). AP003 is a chemically modified, engineered tRNA therapeutic designed to restore full length protein production by inserting the correct amino acid at an Arg-TGA premature termination codon (PTC). It is the first tRNA therapeutic to advance into clinical trials, marking a foundational milestone for the field and for patients with Stop Codon Disease.

"This is the first time an engineered tRNA will be evaluated in humans, marking an important step toward a new way of treating genetic diseases by targeting a shared mutation," said Nerissa Kreher, M.D., Chief Medical Officer of Alltrna. "Initiating this study in Australia allows us to begin generating clinical safety and pharmacokinetic data for AP003, informed by a comprehensive preclinical and toxicology package, as we advance a new modality for patients with Stop Codon Disease. This study begins to establish the clinical foundation to evaluate a single engineered tRNA across diseases that share the same premature termination codon."

In preclinical models, AP003 has demonstrated the ability to restore full-length protein expression and downstream functional activity in disease settings driven by shared PTCs, supporting the biological validity of a mechanism-based approach across genes. Preclinical studies to date show a safety profile that is consistent with established experience for oligonucleotide and lipid nanoparticle-based therapies, supporting clinical evaluation. Together, these data support Alltrna's broader clinical strategy to evaluate AP003 across multiple diseases driven by shared PTCs.

"Establishing initial clinical safety data for a new modality is a critical step to advancing what we believe is the first tRNA approach in the clinic for rare disease patients," Joanne Protano, President and Chief Financial Officer, Alltrna. "This trial enables us to characterize the safety and pharmacokinetics of AP003 and will help inform future clinical evaluation in patients, who today have limited or no treatment options that address the underlying genetic cause of their disease."

The Phase 1 study is designed to evaluate the safety and pharmacokinetics of single ascending doses of AP003 in healthy volunteers. Data from this study are expected to inform subsequent clinical development, including studies in genetically defined patient populations.

About AP003
AP003 is a chemically modified, engineered tRNA oligonucleotide encapsulated in a clinically validated, liver-directed lipid nanoparticle that is in development for the treatment of patients with liver Stop Codon Disease that carry an arginine-to-TGA (Arg-TGA) nonsense mutation in the affected gene. The Arg-TGA variant occurs when a single base of the arginine-encoding codons, CGA and AGA, mutates to UGA (TGA in DNA), a termination codon for which there is no corresponding amino acid. AP003 is designed to read through the premature termination codon to reintroduce arginine into the growing polypeptide chain at the time of RNA-to-protein translation and restore protein production. Arg-TGA is the most frequent nonsense mutation (21-22%) occurring in human genetic diseases.

About Stop Codon Disease
Stop Codon Disease encompasses thousands of rare and common diseases that stem from premature termination codons (PTC) also called nonsense mutations, where the code for an amino acid has been mutated into a premature "stop" codon. This results in a truncated or shortened protein product with no or altered biological activity that causes disease. Approximately 10% of all people with a genetic disease have Stop Codon Disease, representing approximately 30 million people worldwide. Alltrna is engineering tRNA medicines that can read these PTCs and deliver the desired amino acid, thereby restoring the production of the full-length protein.

About Alltrna
Alltrna unlocks tRNA biology to treat disease. The company's platform incorporates AI/ML tools to develop and deliver diverse programmable molecules with broad therapeutic potential. Alltrna has an unprecedented opportunity to advance a single tRNA medicine to readthrough premature stop codons and unify treatment across a wide range of diseases with the same underlying genetic mutations. Alltrna was founded in 2018 by Flagship Pioneering. For more info, visit www.alltrna.com.

Media Contacts
Jessica Yingling, Ph.D., Little Dog Communications Inc., [email protected]
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SOURCE Alltrna