Korro Bio (NASDAQ: KRRO) saw its stock reach its first of two all-time lows, cratering 81% Thursday after reporting disappointing data for its lead pipeline candidate KRRO-110, an RNA editing oligonucleotide being developed to treat alpha-1 antitrypsin deficiency (AATD).
Korro reported data from its Phase I/IIa REWRITE clinical trial (NCT06677307) showing that KRRO-110 generated functional M-AAT protein in AATD patients, but not enough as the company had projected based on preclinical data.
Across five AATD patients in REWRITE’s two single ascending dose (SAD) cohorts evaluable with turbidimetry, the greatest increase of total AAT protein from baseline was approximately 3 µM, while the greatest peak total AAT protein was approximately 10 µM.
Neither of the total AAT protein levels reached 11 µM, the protective threshold considered to be within the asymptomatic carrier range of AAT levels.
The levels achieved by Korro were below the mean AAT levels achieved in clinical trials for competing AATD therapy candidates by two rival developers, Wave Life Sciences (NASDAQ; WVE) and Beam Therapeutics (NASDAQ: BEAM), Myles R. Minter, a partner and research analyst, healthcare, covering biotech companies for William Blair, commented in a research note.
34% workforce cut
Korro responded to the REWRITE results by launching a strategic restructuring that will reduce its workforce by 34%—approximately 30 jobs, based on the roughly 80 jobs the company retained after laying off 20% of its staff in May, when the company cut approximately 20 jobs.
Korro expects to incur about $2.4 million in one-time charges related to the latest restructuring, which is intended to extend the company’s cash runway into the second half of 2027. Korro finished Q3 with $102.5 million in cash, cash equivalents, and marketable securities—down more than one-third (37%) from $163.1 million as of December 31, 2024.
Among the jobs lost is that of chief medical officer Olukemi A. Olugemo, MD, who resigned effective immediately but agreed to serve as an advisor for three months. “Dr. Olugemo’s departure is not related to any disagreement between the parties as to the management of Korro or as to any matter relating to its operations, policies, or practices,” Korro stated in a regulatory filing.
Korro has also pivoted its R&D effort to treating AATD through a GalNAc-conjugated construct set to enter the clinic in 2027.
“We are on track for a potential development candidate nomination in the first half of 2026,” with that candidate expected to enter the clinic in 2027, Ram Aiyar, PhD, Korro’s CEO and president, said in a statement.
In between, during the second half of 2026, Korro expects to advance into clinical trials, KRRO-121, a GalNAc-conjugated construct that is designed to activate a biological pathway by creating a de novo variant, for patients with hyperammonemia.
In nominating KRRO-121 for development, Aiyar said, Korro has taken its first step toward expanding its RNA editing platform beyond protein repair. Korro also emphasized that KRRO-110 generated functional M-AAT protein in AATD patients.
“We’re encouraged by the evidence of clinical activity, which we believe confirms our ability to edit RNA and produce therapeutic proteins in humans,” Aiyad added.
All-time lows
But investors weren’t giving Korro the benefit of the doubt; instead, reacting to the disappointing news with a stock selloff that sent the company’s share price plunging 81% to an all-time low of $6.04 on Thursday at 11:57 a.m. ET before finishing the day at $6.50 and a 79% one-day loss, which worsened to 81% after hours, as the stock slid another 9% to $5.90 at 9:13 p.m.
Korro shares on Friday hit another all-time low of $5.70 before closing at $6.07, for a further 6.6% decline.
A key reason for investors’ quick exit from Korro: The company’s GalNAc-conjugated Serpina1 RNA editing program for AATD would be similar to GalNAc-conjugated Serpina1 RNA editing programs from two rivals, Wave’s WVE-006 and AIR-001 from privately held AIRNA.
“Potential abandonment of KRRO-110 would strip the company of compositional differentiation and advantages associated with Fast Track Designation for KRRO-110 by the FDA,” Minter wrote.
Minter downgraded Korro shares from “Outperform” to “Market Perform.” William Blair was one of at least 10 firms that downgraded their ratings of Korro stock by Thursday, along with:
- Cantor Fitzgerald (Steven Seedhouse, PhD): From “Overweight” to “Neutral,” eviscerating the firm’s price target 92% from $93 to $7.
- Chardan Capital (Keay Nakae, CFA): From “Buy” to “Neutral,” slashing the firm’s price target 72% from $25 to $7.
- Clear Street (Bill Maughan, PhD): From “Buy” to “Hold,” also eviscerating the firm’s price target 92% from $93 to $7.
- C. Wainwright (Mitchell Kapoor): From “Buy” to “Neutral,” without a price target.
- JonesResearch (Catherine Novack): From “Buy” to “Hold,” without a price target.
- Oppenheimer (Andreas Argyrides): From “Outperform” to “Market Perform,” without a price target.
- Piper Sandler (Yasmeen Rahimi, PhD): From “Overweight” to “Neutral,” all but wiping out the firm’s price target 94% from $180 to $11.
- Raymond James (Ryan Deschner, PhD): From “Strong Buy” to “Market Perform,” without a price target.
- RBC Capital Markets (Luca Issi, PhD): From “Outperform” to “Sector Perform,” shredding the firm’s price target 91% from $85 to $8.
“3-2-1” strategy
KRRO-110 was a key component of Korro’s “3-2-1” corporate strategy—three candidates in the clinic, across two tissue types, developed through one platform, Oligonucleotide Promoted Editing of RNA (OPERA®) through 2027.
As a result, Korro placed much hope in its REWRITE trial, a two-part SAD and multiple ascending dose (MAD) study evaluating the safety and tolerability of KRRO-110, including healthy adults and clinically stable AATD patients with the PiZZ genotype.
Korro said it completed all six planned MAD healthy volunteer (HV) cohorts. Each HV cohort consisted of six participants, of which four received active drug and the other two, placebo. Doses of KRRO-110 tested in the 24 HVs included 0.04, 0.1, 0.2, 0.4, 0.8, and 1.2 mg/kg, with the primary aim being to assess safety and tolerability.
KRRO-110 is now being evaluated in two AATD patient cohorts—one of three patients dosed at 0.6 mg/kg, and four patients dosed at 0.8 mg/kg. The AATD patient cohorts are open-label with up to four patients in each cohort.
Korro said it had no current plans to complete additional SAD patient cohorts for KRRO-110, but is evaluating next steps in the MAD portion of REWRITE.
Collaboration pause
The disappointing data also led Korro and Novo Nordisk (NASDAQ Copenhagen: NOVO-B) to pause their up-to-$530 million collaboration to develop two RNA editing product candidates for two undisclosed targets for 12 months. The partnership was designed to combine Novo Nordisk’s cardiometabolic disease and drug development experience with Korro’s platform.
Based in Cambridge, MA, Korro was established in 2018 to commercialize research by Josh Rosenthal, PhD, a neurobiologist at the Marine Biological Laboratory (MBL), whose research into how marine organisms adapt to the physical environment led him to focus on editing RNA transcripts in a cell, potentially altering the proteins produced by that cell.
Rosenthal co-founded Korro with Jean-François Formela, MD, a partner at Atlas Venture focused on novel drug discovery technologies and therapeutics; Nessan Bermingham, PhD; and Andrew Fraley, PhD, a researcher and entrepreneur who is the founder and managing partner at Sunrise BioVentures.
Bermingham is a serial biotech entrepreneur and investor who founded Intellia Therapeutics and previously served as its CEO. He has discussed Korro and other companies he co-founded on GEN’s “Close to the Edge” video series.
Aiyar joined as CEO in 2020. The current Korro took share in 2023 after it completed a reverse merger with Frequency Therapeutics, through an all-stock transaction that included a concurrent $117 million financing, giving the combined company a pro-forma cash balance of about $170 million in cash, cash equivalents, and marketable securities. Last year, Korro raised an additional $70 million through a private investment in public equity (PIPE) financing.
Analysts downgrade Intellia on patient death, safety issues
Intellia Therapeutics (NASDAQ: NTLA) announced positive clinical results for two of its key pipeline programs this past week at a pair of scientific conferences. But those readouts did little to sway either analysts or investors, all still reeling from the company’s November 7 announcement that an elderly patient in its Phase III MAGNITUDE trial (NCT06128629) assessing nexiguran ziclumeran (nex-z; formerly NTLA-2001) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM) died a week after being hospitalized with liver dysfunctions.
The death occurred two days after the FDA imposed a clinical hold on the Investigational New Drug (IND) applications of both MAGNITUDE and a second 47-patient Phase III study of nex-z called MAGNITUDE-2 (NCT06672237). The clinical hold came two days after Intellia voluntarily paused dosing and screening in both trials.
Intellia shared better news this past week on lonvoguran ziclumeran (lonvo-z; formerly NTLA-2002), an in vivo CRISPR-based gene editing therapy being developed as a one-time treatment for hereditary angioedema (HAE). The company announced follow-up data showing what it called deep, stable, and durable reductions of plasma kallikrein in all 32 patients who received a 50 mg dose of the therapy, according to a pooled analysis of data from an ongoing Phase I/II trial (NCT05120830) of lonvo-z.
Of the 32 patients, all but one (97%) were attack-free and long-term prophylaxis (LTP)-free, Intellia said, while 24 patients (75%) were attack-free and LTP-free for seven to 32 months. And among the 11 patients who originally received a 50 mg dose in the study’s Phase II portion, 10 were attack-free and LTP-free. The 11th patient showed a 59% reduction from baseline in their monthly attack rate.
“In HAE, NTLA-2002 [lonvo-z] clinical data to date suggest best-in-class efficacy and a functional cure for the majority of patients—setting the stage for it to be the first approved in vivo CRISPR therapy in a large and growing rare disease market with attractive reimbursement,” Mani Foroohar, MD, a senior research analyst with Leerink Partners focused on genetic medicines, wrote in a research note.
Intellia presented its positive data for lonvo-z at the American College of Allergy, Asthma & Immunology (ACAAI) 2025 Annual Scientific Meeting in Orlando, FL.
Intellia president and CEO John Leonard, MD, stated that Intellia plans to report additional clinical data next year on lonvo-z—namely, a topline readout from the company’s Phase III HAELO trial (NCT06634420), planned by mid-2026. Intellia has said it expects to submit a Biologics License Application (BLA) in the second half of 2026 and potentially launch lonvo-z in 2027 in the United States.
“Today’s data further support our belief that lonvo-z could completely redefine the HAE treatment landscape,” Leonard said.
Long-term nex-z data
Intellia also reported positive long-term data from its ongoing Phase I trial (NCT04601051) of nex-z in ATTR-CM, showing that a one-time treatment of nex-z led to consistently rapid, deep, and durable reduction in serum TTR through three years of follow-up.
During a late-breaking oral presentation at the American Heart Association (AHA) Scientific Sessions 2025 in New Orleans, Intellia showed that among nine patients who reached 36 months of follow-up, the mean serum TTR reduction was 87% (mean absolute serum TTR level of 22.9 µg/mL), consistent with the overall cohort at month 24.
Also at 24 months, two markers associated with disease progression (NT-proBNP and hs-Troponin T) showed stability or improvement in 70% and 85% of patients, respectively. Preservation of functional status, as measured by 6MWT, was seen with 69% of patients either showing stability or improvement, while 81% of patients were stable or improved in their New York Heart Association (NYHA) classification at 24 months, including improvement in 83%Â of patients with NYHA Class III.
A post-hoc mortality assessment showed that patients receiving a one-time treatment with nex-z had an all-cause mortality rate of 3.9 per 100 patient-years, compared with 12.7 per 100 for a cohort of 1,792 ATTR-CM patients from the National Amyloidosis Center whose baseline characteristics were matched to those of the Phase I trial’s nex-z population.
“It’s remarkable that even in patients with advanced heart failure, a population that declines rapidly, disease stabilization or improvement was observed out to 24 months in a majority of participants. We look forward to seeing how these data mature in longer-term follow-up,” Leonard added.
The positive data from nex-z and lonvo-z appeared to have little effect in slowing down Intellia’s price decline. Intellia finished the week down 9%, tumbling to $8.70 at Friday’s close from $9.52 a week earlier, on continuing concerns about the safety of nex-z.
“Serious hurdles”
“We believe there are serious hurdles the company needs to address in the coming months,” Brian Cheng, an executive director and senior biotech analyst with J.P. Morgan, wrote in a research note. “The hurdles, in our view, assuming the end goal is understanding the cause behind the liver tox events, will not be easy to overcome, nor will the process be a short one.”
Cheng downgraded Intellia from “Neutral” to “Underweight” and lowered his firm’s price target on the company’s shares by 58%, from $12 to $5. He cited, in part, concerns about what he estimated were four more Grade 4 liver toxicity cases beyond the two that Intellia has disclosed, based on a company statement that “less than 1%” of the 650 patients enrolled in MAGNITUDE had Grade 4 liver transaminase elevations. Cheng also cited greater use of capital raised through an at-the-market financing than Intellia had previously disclosed.
“Given the lack of clarity on the regulatory, clinical, financing, and commercial aspects stemming from Intellia’s key value driver today, we are moving to an UW [underweight] rating,” Cheng wrote.
Joining Cheng in downgrading Intellia shares this past week was Evercore ISI, where Jonathan Miller, PhD, a managing director, biotech and pharma equity research, lowered his firm’s rating from “Outperform” to “In-Line” and cut its price target by 53%, from $17 to $8.
Miller acknowledged “very promising efficacy updates” but cited uncertainty around the timeline of the ATTR program in light of the clinical hold’s timeline, despite acknowledging Evercore noted that there’s a “path to value”—albeit a narrower, riskier one—and said that clarity could come with the HAELO results expected next spring.
At JonesTrading, Debanjana Chatterjee, PhD, a senior analyst on the firm’s healthcare research team, downgraded Intellia from “Buy” to “Hold,” while Wolfe Research’s Andy Chen, PhD, a director and senior analyst, lowered his firm’s rating from “Outperform” to “Peer Perform.”
At least 10 other investment firms lowered their price targets on Intellia shares:
- Baird (Jack K. Allen): Down 56% from $9 to $4 on November 7, maintaining “Neutral” rating.
- Chardan Capital Markets (Geulah Livshits, PhD): Down 46% from $48 to $26 on November 7, maintaining “Buy” rating.
- Truist Securities (Joon Lee, MD, PhD): Down 44% from $25 to $14 on November 10, maintaining “Buy” rating.
- Barclays (Gena Wang, PhD, CFA): Down 42% from $24 to $14 on November 7, maintaining “Overweight” rating.
- RBC Capital Markets (Luca Issi, PhD): Down 36% from $14 to $9 on November 7, maintaining “Sector Perform” rating.
- Wells Fargo Securities (Yanan Zhu, PhD): Down 29% from $17 to $12 on November 7, maintaining “Hold” rating.
- Citizens JPM (Silvan Tuerkcan, PhD): Down 28% from $29 to $21 on November 7, maintaining “Market Outperform” rating.
- Wedbush Securities (David Nierengarten, PhD): Down 22% from $9 to $7 on November 7, maintaining “Neutral” rating.
- Oppenheimer (Jay Olson): Down 18% from $33 to $27 on November 7, maintaining “Buy” rating.
- H.C. Wainwright (Mitchell Kapoor): Down 17% from $18 to $15 on November 10, maintaining “Buy” rating.
Leaders and laggards
- Anavex Life Sciences (NASDAQ: AVXL) shares nosedived 36% from $5.69 to $3.65 Friday after the developer of treatments for central nervous system disorders acknowledged that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) carried out a negative trend vote on the company’s Marketing Authorization Application (MAA) for its early Alzheimer’s disease candidate blarcamesine. The CHMP is expected to adopt a formal opinion on the MAA next month. Anavex said it intends to request a re-examination of the CHMP opinion upon formal adoption, including providing relevant biomarker data, based on feedback and continued guidance from the CHMP, EMA, and the Alzheimer’s disease community. Anavex also said it has been advised by the FDA’s Center for Drug Evaluation and Research to request a meeting to discuss the company’s Alzheimer’s disease clinical trial results.
- Cypherpunk Technologies (formerly Leap Therapeutics; NASDAQ: LPTX) shares nearly quintupled, catapulting 369% from 44 cents to $2.05 on Wednesday after the cancer therapy developer announced a pivot of its business to a digital asset treasury strategy aimed at accumulating the privacy-preserving blockchain Zcash’s native coin ZEC. Cypherpunk’s ongoing cancer research and development operations will be conducted under a wholly-owned subsidiary to be named Leap Therapeutics. Cypherpunk also announced the appointment of Khing Oeias to board chairman—succeeding Christopher Mirabelli, PhD, who stepped down—and Will McEvoy as the company’s first-ever chief investment officer. As part of its rebranding, Cypherpunk plans to change its ticker symbol to CYPH.
