Wave Life Sciences' breakthrough clinical trial data, demonstrating the potential of RNA-editing therapies, has triggered a surge in the stock prices of companies developing similar treatments. The positive results from Wave's single-dose trial for a genetic disorder affecting the lungs and liver have been hailed as a landmark moment for the RNA-editing field, validating the technology's promise.
Proof-of-Mechanism Achieved
Wave Life Sciences Ltd. announced that it had achieved proof-of-mechanism in a Phase Ib/IIa trial (RestorAATion-2, NCT06405633) of its candidate WVE-006 for alpha-1 antitrypsin deficiency (AATD). The data showed successful editing of mutant Z-AAT mRNA, leading to the presence of wild-type alpha-1 antitrypsin (M-AAT) protein in patients with Pi*ZZ AATD. Investors responded favorably, driving Wave's stock up by as much as 82%, adding approximately $960 million to the company's market capitalization.
"This is the first time we’ve seen it in humans actually do what we think it’s doing," said Madison El-Saadi, an analyst at B Riley Securities, highlighting the significance of the findings. "The fact that we see this with just one dose, it is really promising."
Industry-Wide Impact
The positive data from Wave Life had a ripple effect across the RNA-editing sector, with other companies experiencing substantial stock gains. ProQR Therapeutics NV shares climbed as much as 117%, while Korro Bio Inc. shares more than doubled, soaring as much as 146%.
Luca Issi, an analyst at RBC Capital Markets, noted, "We think WVE data is fantastic news for the broader field," underscoring the widespread optimism surrounding the RNA-editing space.
AATD and the Promise of RNA Editing
Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that can lead to lung and liver diseases. Wave Life's WVE-006 is designed to correct the single-base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, enabling restoration and circulation of functional M-AAT protein. The trial data revealed increases in total AAT from baseline and M-AAT protein as early as day 3, with circulating wild-type M-AAT protein in plasma reaching a mean of 6.9 micromolar at day 15, representing more than 60% of total AAT.
Korro Bio's Approach
Korro Bio, another key player in the RNA-editing space, is also focused on treating AATD with its lead candidate KRRO-110. Preclinical data for KRRO-110 has demonstrated AAT levels between MM and MZ in rodents as early as week 1, a rapid reduction in mutant “Z” aggregates and Z-AAT protein, and no off-target effects. Korro anticipates filing an Investigational New Drug (IND) application with the FDA by the end of the year to initiate clinical trials of KRRO-110.
ProQR's Differentiated Platform
ProQR Therapeutics is developing RNA therapies for severe rare and common diseases based on its Axiomer™ platform. The company plans to advance its two lead candidates, AX-0810 (for cholestatic diseases) and AX-1412 (for cardiovascular disease), into clinical trials in late 2024 to early 2025. ProQR also has an ongoing collaboration with Eli Lilly to target disorders of the liver and nervous system.
Future Outlook
Wave Life plans to report data from a multi-dose trial of its therapy in 2025. The company's success has not only boosted its own prospects but has also invigorated the entire RNA-editing field, paving the way for potential new treatments for a range of genetic diseases.
