After becoming the first group to therapeutically edit human RNA in October 2024, Wave Life Sciences has released more data from its ongoing alpha-1 antitrypsin deficiency (AATD) clinical trial—and investors appear less enthusiastic this time around.
Patients in the 200-mg single-dose, 200-mg multidose and 400-mg single-dose cohorts of Wave's phase 1b/2a trial all achieved “therapeutically relevant” levels of AAT, the company announced Sept. 3.
Despite the trial win, the biotech’s stock toppled from $9.48 per share at the end of Tuesday to $7.82 by 3 p.m. ET on Wednesday, Sept. 3, representing an 18.6% decline.
Rival biotech Beam Therapeutics, meanwhile, enjoyed a stock bump from $16.37 per share at Tuesday's end to $18.31 by 3 p.m. ET the next day, climbing 12%.
“We have demonstrated the potential for WVE-006 to achieve a long-standing goal by restoring expression of AAT under endogenous physiologic control,” Wave President and CEO Paul Bolno, M.D., said in the release. “Furthermore, these data support monthly or less frequent dosing. Collectively, our data highlight WVE-006’s potential to provide a transformative treatment option for people living with AATD.”
Wave’s ongoing phase 1/2 RestorAATion-2 trial currently has 24 patients enrolled to test GSK-partnered WVE-006, an RNA-editing oligonucleotide designed to correct the Pi*ZZ mutation that commonly causes severe AATD. While Beam’s one-time approach targets the mutated DNA itself, Wave is instead pursuing the mRNA that is created from the gene, meaning patients would need to continuously take the medication.
Adverse events seen so far were mild to moderate, Wave said in the release, with no treatment discontinuations.
Wave’s stock slide may be explained by investors hoping AAT levels would be even higher, analysts from Mizuho wrote in a Sept. 3 note, even though WVE-006’s results are “still clinically meaningful and hitting the potential regulatory bar.”
The highest AAT levels first reported by Wave last October, which sent the company’s stock price soaring up 63%, reached 10.8 micromolar. In the new data drop, Wave presented average levels of 11.8 micromolar for the single 200-mg dose group, excluding an outlier with a kidney stone who reached an abnormally high 20.6 micromolar, and 12.8 micromolar in the single 400-mg dose group. Patients in the 200-mg multidose cohort reached AAT levels of 11.9 micromolar.
“Investors from our conversations over the last few months didn't have a clear quantitative bogey, just wanted it higher than the prior reported 10.8,” the Mizuho analysts wrote. “All things considered, we got that here.”
Analysts from Leerink Partners agreed in a separate Sept. 3 note, nothing that "competitor Beam's data seemed to level out around 12 micromolar despite increasing doses and higher levels of editing."
"We think investors should take advantage of this weakness to buy the stock ahead of additional important catalysts, which we remain optimistic investors will appreciate despite today's confusion," the Leerink analysts wrote.
In AATD, patients lack a critical liver enzyme that helps prevent vital proteins from being degraded due to mutations in the SERPINA1 gene. Lack of AAT leads to liver symptoms like cirrhosis, but, because the enzyme normally migrates to the lungs, the disease can also cause lung-related complications like chronic obstructive pulmonary disease.
Once the RestorAATion-2 trial wraps up, GSK will take over clinical development and commercialization of WVE-006 under the pact the Big Pharma signed with Wave in December 2022. That deal saw GSK pay Wave $120 million in cash and a $50 million equity investment upfront, along with a potential $525 million in milestones.