RNA editing oligonucleotide selected for AATD treatment 

Oligonucleotide

Korro Bio, a biopharmaceutical company focused on developing a new class of genetic medicines for both rare and highly prevalent diseases, has nominated its first development candidate, KRRO-110, for the potential treatment of alpha-1 antitrypsin deficiency (AATD).  

KRRO-110 is an RNA editing oligonucleotide delivered to liver cells using clinically validated lipid nanoparticle (LNP) technology licensed from Genevant. KRRO-110 is designed to co-opt an endogenous enzyme Adenosine Deaminase Acting on RNA (ADAR) to repair a pathogenic single nucleotide variant (SNV) on RNA and restore production of normal A1AT. Preclinical development of KRRO-110 is ongoing in preparation for a potential regulatory filing in the second half of 2024. 

“The advancement of KRRO-110 highlights the power of our RNA editing platform, OPERA, and we are excited to see what we expect to be the first of many candidates move into the clinic over the coming years,” said Dr Ram Aiyar, Chief Executive Officer of Korro. “Selecting a development candidate for our AATD program is an important milestone for Korro, but more importantly, for patients. We are confident that the preclinical profile demonstrated by KRRO-110 will make it a potentially game-changing therapeutic candidate that reduces the disease burden and addresses the continued unmet need faced by patients with both liver and lung manifestations of AATD.” 

Context and treatment potential 

AATD is an inherited, autosomal recessive genetic disorder that is most frequently caused by a single nucleotide variant (SNV) mutation in the SERPINA1 gene, the most common of which is the ‘PiZ’ mutation. Greater than 95% of severe clinical cases are homozygous for the PiZ mutation (known as the PiZZ genotype).  

Korro has generated preclinical data demonstrating high editing efficiency (>50% editing), which it believes is a key threshold to achieving clinically meaningful secretion of normal A1AT protein in an in vivo mouse model, and targeted durability.  

In addition, Korro has also shown using surrogates that its product candidates have high translation of RNA editing efficiency from mice to non-human primates (NHPs), demonstrating the potential applicability of its approach in humans. 

“AATD patients face a critical unmet need given the limited effectiveness of current standard-of-care options for either the liver or the lung manifestations of the disease,” said Dr Jeffrey Teckman, an expert in AATD from St Louis University School of Medicine and a long-time advisor to Korro. “Korro’s RNA editing approach has the potential to be transformative for AATD patients and Korro is well-positioned to deliver a best-in-class therapeutic. I look forward to having access to this therapy as quickly as possible.” 

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