Wave Life Sciences (WVE) was not the only developer of RNA editing therapies to show significant stock gains from its historic proof-of-mechanism for its RNA editing platform, shown recently in the first-ever clinical demonstration of RNA editing in humans.
With RNA editing rapidly gaining momentum among researchers and companies, Wave made genetic medicine history on Wednesday. The company announced that its alpha-1 antitrypsin deficiency (AATD) candidate WVE-006 showed positive confirmation of successful editing of mutant Z-AAT mRNA in the Phase Ib/IIa RestorAATion-2 trial (NCT06405633), as evidenced by the presence of wild-type alpha-1 antitrypsin (M-AAT) protein in two patients with “ZZ” AATD (Pi*ZZ AATD).
Investors roared their approval of Wave’s RNA editing data by sending the company’s shares skyrocketing 74% from $8.56 to $14.90 on Wednesday. The stock dipped 2% to $14.61 Thursday before rebounding Friday, rising 5% to $15.31.
Investors were wowed by Wave’s reported increases in total AAT from baseline and M-AAT protein that were seen as early as day 3 and through day 57. According to the data Wave shared, circulating wild-type M-AAT protein in plasma reached a mean of 6.9 micromolar at day 15, representing more than 60% of total AAT.
“We thought that repeat dosing might be required for these kinds of levels to be reached, based on management’s positioning. However, WVE’s goal for any amount of M-AAT protein to be produced in PiZZ AATD patients as evidence of successful RNA editing (since they produce no normal protein) has now been handily beat,” Joseph P. Schwartz, an analyst with Leerink Partners specializing in biopharma and rare diseases, wrote Wednesday in a research note. Schwartz raised his firm’s 12-month price target on Wave’s shares 10%, from $20 to $22.
“We believe [Wednesday]’s proof-of-mechanism data provide robust demonstration of ADAR RNA editing in humans and provides clinical validation of WVE’s RNA editing platform as well as proof-of-concept for the rest of WVE’s wholly-owned pipeline of RNA editing candidates,” Schwartz added.
Best-ever one day gains
Two other public companies focused on RNA editing therapies showed even more impressive stock surges powered by their best-ever one-day gains as their share prices were lifted by Wave’s clinical milestone.
Korro Bio (KRRO) shares nearly doubled late last week, leaping 94% from $39.76 Tuesday to an even $77 Wednesday. Shares climbed another 4% Thursday to $80.01, then barely blipped up 0.04% to $80.04 Friday.
Korro is a developer of RNA-edited therapies also focused on treating AATD, via its lead candidate KRRO-110. During the 20th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in Montreal, Korro presented positive preclinical data for KRRO-110 showing it achieved AAT levels between MM (normal AAT genes from each parent) and MZ (normal gene from one parent, mutant gene from another) in rodents as early as week 1, a rapid reduction in mutant “Z” aggregates and Z-AAT protein, and no off-target effects.
Korro said over the summer it would file an Investigational New Drug (IND) application with the FDA seeking to begin clinical trials of KRRO-110 by year’s end.
In its corporate presentation earlier this month, Korro said it had a sufficient cash “runway” to operate into the second half of 2026, which will enable an interim readout from its planned Phase I/II trial of KRRO-110 in “ZZ” AATD patients in the second half of next year, with completion of the study anticipated in 2026. Korro improved its finances when it raised $117 million in financing from a syndicate of top-tier investors last year, on top of the $116 million it raised in private Series B financing in 2022 before going public via a reverse merger with Frequency Therapeutics.
Korro has one other potential financial advantage over Wave: It is developing its RNA edited therapies alone rather than having to share up to 80% of revenue with GlaxoSmithKline (GSK), with which Wave is partnering in the development of WVE-006 under an up-to-$3.3 billion collaboration launched in December 2022.
Under that collaboration, Wave and GSK agreed to partner on WVE-006 and launch a discovery collaboration under which GSK would advance up to eight programs, while Wave would advance up to three. The companies say they both benefit from their partnership since it combines Wave’s PRISM platform with GSK’s expertise in genetics and genomics.
“Better way to play RNA editing”
“While we acknowledge WVE is ahead, we continue to believe that KRRO is the better way to play RNA editing given unconstrained economics (vs 80%+ of WVE revenue going to GSK) and what we argue is a better editing efficiency at lower doses,” RBC Capital Markets analysts Luca Issi, PhD, and Lisa Walter, PhD, wrote Wednesday in a research note.
The analysts based their efficiency argument on Korro showing editing efficiency of 50%, rising to 60% after five injections of its RNA-edited therapy.
“We would be buyers into strength,” Issi and Walter added.
Yet the RBC Capital Market analysts also cited several strengths seen in Wave’s data: Its editing platform works quickly, they concluded, based on increases in AAT seen after three days, rising to 10.8 uM after 15 days compared with baseline when Wave measured “LLOQ,” the lowest limit of quantification. Issi and Walter also acknowledged that Wave’s technology was durable since the effects were seen up to 57 days, and showed high efficiency since more than 60% of total AAT measured was wild type.
Another Wave competitor, ProQR Therapeutics (PRQR), saw its share price Wednesday more than double, catapulting 122% from $1.81 to $4.02. The stock jumped another 12% to $4.49 before declining 4% to $4.33 Friday.
ProQR—one of GEN’s “Companies to Watch” among RNA-based biopharmas back in 2021—develops RNA therapies for severe rare and common diseases based on its Axiomer
platform, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression.
Responding to the news from Wave, ProQR publicly highlighted some of its key differentiators in RNA editing, including:
- Plans to advance its two lead candidates, which are on track to enter the clinic in late 2024 to early 2025—AX-0810, designed to treat cholestatic diseases by targeting NTCP; and AX-1412, indicated for cardiovascular disease by targeting B4GALT1.
- Broad applicability of its Axiomer platform across a range of diseases, including in the central nervous system.
- The ability to show proof of target engagement in healthy individuals, bypassing the need to wait for patient studies.
Another strength, according to ProQR, is its ongoing collaboration with Eli Lilly to target disorders of the liver and nervous system by applying the Axoimer platform, launched in 2021 and expanded in 2022 into a potential nearly $4 billion agreement.
That sum consisted of an initial $75 million (upfront payment plus equity investment); a $50 million option Lilly can exercise to expand the partnership further; up to approximately $3.75 billion in payments tied to achieving research, development, and commercialization milestones; and tiered royalties of up to mid-single digit percentage on product sales.
Wave of enthusiasm
At deadline, at least one investment firm responded to Wave’s RNA editing milestone by upgrading their ratings of the company’s stock. Steven Seedhouse, PhD, managing director, head of biotechnology research with Raymond James, revised the firm’s rating from “Outperform” to “Strong Buy.” Seedhouse also more than doubled Raymond James’ price target on Wave shares, lifting it 69% from $13 to $22.
Raymond James and Leerink were two of at least four investment firms that have raised their price targets on Wave shares in recent days. The others were:
- J.P. Morgan (Eric Joseph)—Up 31%, from $13 to $17, maintaining the firm’s “Overweight” rating.
- Wells Fargo (Tiago Fauth)—Doubled from $11 to $22, maintaining the firm’s “Buy” rating.
Salim Syed, managing director, senior biotechnology analyst with Mizuho Securities, confirmed Wave’s claim to RNA editing history, observing in a research note wrote that, “This is the first clinical data point for RNA editing (from Wave Life Sciences or any others, as far as we know) and proof-of-mechanism for the platform,” Syed wrote. Syed has given Mizuho’s “Outperform” rating to Wave shares and has set a $19 price target.
Syed also noted that the patients whose positive data was announced by Wave are individuals who are homozygous for the SERPINA1 Z mutation “ZZ” AATD (Pi*ZZ AATD). WVE-006 is designed to correct the single-base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby enabling restoration and circulation of functional M-AAT protein.
“Therefore any production (of AAT protein) at all is proof-of-mechanism,” Syed added.
Leaders and laggards
- Gritstone Bio (GRTS) shares slid 14% from $0.70 to $0.60 Wednesday following a news report quoting a lawyer for the company as saying it is in talks to secure funding: “We have had some conversations with several parties that might be interested in being a plan sponsor” who could “keep the company alive,” Debra Grassgreen, a lawyer at Pachulski Stang Ziehl & Jones, told Bloomberg Law. Gritstone on October 10 voluntarily filed for Chapter 11 protection from creditors in U.S. Bankruptcy Court for the District of Delaware (Case No. 1:24-bk-12305). U.S. Bankruptcy Court Judge Karen B. Owens has approved Gritstone’s request to pay wages and vendors using cash collateral.
- MeiraGTx Holdings (MGTX) shares soared 39% over three days, from $4.25 October 11 to $5.92 Wednesday, a day after the company announced positive topline data from its Phase I/II MGT-GAD-025 (NCT05603312) clinical bridging study of AAV-GAD gene therapy for the treatment of Parkinson’s disease. At week 26, MeiraGTx said, AAV-GAD showed a statistically significant 18-point average improvement from baseline in UPDRS Part 3 “off” medication score in the five-patient high dose group, with no significant change in the low-dose group (5 patients) or the four patients receiving a sham surgical procedure. In the high dose group, the Parkinson’s Disease Questionnaire (PDQ-39) score of patients improved by 8 points from baseline, the low-dose group improved by 6 points, while the sham surgery patients’ score worsened by 0.2 points, a result deemed not statistically significant.
- Novavax (NVAX) shares skidded 19% from $12.60 to $10.15 Wednesday after the company said the FDA had placed a clinical hold on the company’s Investigational New Drug (IND) application for its COVID-19-Influenza Combination (CIC) and stand-alone influenza vaccine candidates. Novavax said the clinical hold followed a spontaneous report of a serious adverse event (SAE) of motor neuropathy in a single participant in the Phase II CIC trial (NCT05519839) outside of the United States who received the vaccine in January 2023. While the trial ended in July 2023, the participant had not reported the SAE until last month. The IND for Novavax’s COVID-19 vaccine is not impacted by the clinical hold.
- Seelos Therapeutics (SEEL) shares nosedived 48% from $2.45 to $1.28 Tuesday, after the company acknowledged that the Nasdaq Hearings Panel decided to delist the company’s common stock from the Nasdaq Stock Market due to Seelos’ failure to comply by October 11 with the exchange’s minimum stockholder’s equity requirement. As of Wednesday, trading in the common stock was suspended and Seelos shares began trading on the OTCQB® Venture Market, where shares fell 9% Wednesday to $1.17, then tumbled another 14% to $1.01 Thursday as of 1:09 p.m. ET. OTCQB is an over-the-counter exchange that requires listing companies to be current in their reporting, meet the $0.01 bid test, and not be in bankruptcy.
The post StockWatch: Wave’s RNA Editing Milestone Lifts Korro, ProQR appeared first on GEN – Genetic Engineering and Biotechnology News.
