Two months after laying off 20% of its staff, Korro Bio says it has not retreated from its ambitious slogan, “Edit the message. Rewrite the future,” or from its corporate strategy, which the developer of RNA-edited therapies sums up as “3-2-1.” That’s three candidates in the clinic, across two tissue types, developed through one platform, Oligonucleotide Promoted Editing of RNA (OPERA®) through 2027.
One of those candidates, its lead pipeline asset KRRO-110 for alpha-1 antitrypsin deficiency (AATD), is an RNA editing oligonucleotide being developed to treat alpha-1 antitrypsin deficiency (AATD). KRRO-110 is well into a Phase I/IIa trial set to read interim data later this year. Also, before the end of 2025, Korro plans to nominate a second clinical candidate for a liver-targeting program designed to treat an undisclosed rare metabolic disorder.
To fund those programs toward key inflection points, plus nominate its second clinical candidate and advance its up-to-$530 million collaboration with Novo Nordisk, Korro in May eliminated approximately 20% of its workforce. That amounted to some 20 jobs, based on the 104-person full-time workforce it reported employing as of December 31, 2024, according to its most recent Form 10-K annual report, filed March 18.
“We went from being a preclinical company with a novel technology to a clinical company,” Ram Aiyar, PhD, Korro’s CEO and president, told GEN Edge. “We need to allocate resources in areas where we are going to drive value for the company.”
That allocation process was carried out after Korro hired Loïc Vincent, PhD, as the company’s CSO. Vincent previously held the same position at Affini-T Therapeutics and earlier served as an executive at several biopharmas including Takeda Pharmaceutical and Sanofi.
“He put his arms around the research team, figured out skill sets, and then we—I don’t want to say we eliminated jobs, but we consolidated skill sets and combined a few skill sets as needed. So instead of two people, we can get one person that has both people’s skill sets,” Aiyar said.
Korro also acted to cut its expenses, Aiyar continued, after financial markets turned bearish last spring. While the company took a one-time restructuring charge against second-quarter earnings of approximately $1.2 million, including employee severance, benefits, and related termination costs, Korro extended its financial runway from the second half of 2026 into 2027 through the restructuring.
Controlling burn
“I am confident that our data is going to be good. But if our data is good and the markets are not in a good spot, then for me to think about financing and supporting the company is going to be challenging. So, the only way that I know what I can control is burn,” Aiyar said, referring to the speed at which companies spend cash to fund operating expenses and capital expenditure requirements.
“Last year, we had a burn of $83 [million] to $85 [million], and that’s including construction costs as we moved into a new place,” he said. Korro Bio last year opened a new headquarters occupying more than 50,000 square feet at 60 First St., in the Kendall Square section of Cambridge. “So, I think that we’re trying to be very thoughtful in terms of how we allocate capital going forward,” Aiyar added.
Another reason why Korro is concerned about burn: The company ended the first quarter with cash, cash equivalents, and marketable securities of $138.992 million, down roughly 15% from $163.054 million at the end of 2024.
To its credit, however, Korro has been meeting its timelines for advancing KRRO-110 toward key proof-of-concept data that could validate the company’s OPERA platform in ADAR-mediated RNA editing, Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote in a research note to investors.
“We believe Korro possesses potential best-in-class preclinical data for boosting corrected AAT levels in AATD, and that the RNA editing approach can provide a transient and dose-titratable option in the genetic medicine space that may avoid the potential risk of permanent off-target DNA editing,” Minter wrote.
Through OPERA, Korro uses a proprietary engineered oligonucleotide to introduce precise edits in RNA through a single base change. By precisely and transiently editing the genetic mutation in RNA rather than permanently altering DNA, Korro reasons that it can avoid harmful effects of permanent DNA-based genome editing, such as off-target edits.
For patients, Korro says, OPERA-created treatments will deliver the functional benefits of gene therapy with a transient, titratable, and specific treatment regimen, thus advancing genetic medicines beyond rare genetic diseases into more common diseases affecting larger patient populations.
Korro is among a small but growing number of companies focused on developing therapies for AATD, an inherited genetic disorder in which patients fail to produce enough of the alpha-1 antitrypsin protein to protect their lungs and allow them to function normally.
Furthest along among those companies are two that are set to release updated Phase I/II data later this year: Wave Life Sciences, whose lead candidate WVE-006 is a subcutaneously-dosed GalNAc-conjugated A-to-I RNA editing oligonucleotide designed to treat AATD; and Beam Therapeutics, which is targeting the disease through its in vivo base editing therapy BEAM-302, a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to correct the E342K point mutation (PiZZ genotype) through a single treatment.
Initial data
In April, Beam presented initial safety and efficacy data from its Phase I/II dose exploration and dose expansion trial (BTX-302-001; NCT06389877) showing that within a three-patient cohort dosed at 60 mg, the proportion of corrected wild-type alpha-1 antitrypsin (M-AAT) protein having reached a mean of 91% of total AAT in circulation at day 28 following treatment with BEAM-302, with a mean decrease of 79% in mutant AAT protein (Z-AAT). That data emerged a month after Beam announced positive initial safety and efficacy data that it said established clinical proof of concept as a potential treatment for AATD and in vivo base editing.
Last October, Wave announced that WVE-006 showed positive confirmation of successful editing of mutant Z-AAT mRNA in the Phase Ib/IIa RestorAATion-2 trial (NCT06405633), as seen by the presence of M-AAT protein in two patients with “ZZ” AATD (Pi*ZZ AATD).
“At its highest dose tested, BEAM-302 showed higher M-AAT protein level vs WVE-006 at the lowest dose, but WVE will likely achieve similar, if not better, M-AAT level at higher doses,” Roger Song, MD, an equity research analyst with Jefferies, wrote in a research note. Song also cited the potential of off-target editing with BEAM-302—a risk Beam has cautioned is significant in any base editing product candidate, though adding that it has never had an off-target edit that had a material adverse impact on the safety or benefit of its candidates.
Song added that WVE-006 has shown similar editing efficiency to KRRO-110, which is being studied in the Phase I/IIa REWRITE trial (NCT06677307), a first-in-human single ascending dose (SAD) and multiple ascending dose (MAD) escalation study.
REWRITE is designed to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of KRRO-110. REWRITE is assessing KRRO-110 in a total of 60 participants—36 healthy adult volunteers and 24 clinically stable adults with AATD (16 in the MAD portion, eight in the SAD portion). The primary endpoint is the type, frequency, and severity of treatment-emergent adverse events.
Korro says it’s on track to complete the REWRITE trial in 2026, from which the company plans to read out interim results later in the second half of this year.
Recently, the European Medicines Agency (EMA) granted its orphan drug designation to KRRO-110 in AATD, four months after the treatment candidate received a similar designation from the FDA.
“This year, I think our goal is to showcase that the mechanism works, that we have a reasonably good drug, that there is a dose response that comes together, and that safety is going to be paramount. I think if we can show those four things, that puts us in the driver’s seat,” Aiyar said. “When you think about the relative speed with which we have gone, we’ve actually made progress very, very quickly.”
Second clinical nomination
By year’s end, Korro plans to nominate its second clinical candidate, a program designed to treat an undisclosed rare metabolic disorder via conjugation of GalNAc (N-acetylgalactosamine), a sugar molecule that can recognize and bind to a cell surface protein, the asialoglycoprotein receptor (ASGPR), which is abundantly expressed on liver cells.
A third potential clinical candidate could emerge in amyotrophic lateral sclerosis (ALS). Korro has a preclinical-phase program aimed at developing oligonucleotides targeting messenger RNA (mRNA) for TAR DNA binding protein 43 (TDP-43), which is associated with the development of ALS.
While the ALS candidate is likely to reach the clinic, Korro has not discussed when that is likely to happen.
“Obviously, ALS is a pretty devastating disease. But the development path is quite challenging in terms of how you think about it,” Aiyar acknowledged. “Investors are like, not so super excited about it. But we as a company are super excited about it because it could have a huge impact on those patients. So trying to thread that needle [of timing to the clinic] is going to be important.”
Korro’s pipeline includes a program designed to treat a subset of pain. Korro has a discovery phase program to develop oligonucleotides designed to selectively modulate ion channels associated with pain. Specifically, Korro’s program aims to selectively block NaV1.7, a targeted approach intended to provide more effective and safer pain management options compared with several classes of drugs, including local anesthetics.
Also in Korro’s pipeline are two candidates being developed through the up-to-$530 million collaboration with Novo Nordisk, designed to develop RNA editing product candidates for two undisclosed targets by combining Novo Nordisk’s cardiometabolic disease and drug development experience with Korro’s platform. The first target is intended to treat cardiometabolic diseases with high prevalence; the companies have not shared the therapeutic area to be targeted by the second.
The companies are not discussing their progress to date. As of March 31, according to its Form 10-Q report for the first quarter, Korro received from Novo Nordisk $10 million upfront and recognized $2.55 million in collaboration revenue during Q1. The transaction price to date includes the upfront money and $30.1 million reimbursed to Korro for estimated research services for the first target.
Connecting the dots
Aiyar credits Uli Stilz, PhD, now Novo Nordisk corporate vice president, research & early development focused on external innovation partners, external & exploratory innovation (E2I) with helping bring the companies together based on his company’s interest in pursuing technology that can build upon the capabilities Novo Nordisk bought when it acquired Dicerna Pharmaceuticals in 2021 for $3.3 billion—a deal that married the partners in a three-year-old RNA interference (RNAi) drug collaboration.”
“He can connect the dots better than most people, and so at some point in time there was a light bulb in terms of, Ohh you’re trying to activate biological pathways,” Aiyar said of Stilz, who was promoted last month after more than six years as head of Novo Nordisk’s Bio Innovation Hub in Cambridge, MA. “I said OK, I don’t want to do a 10-target deal. I don’t want to spend a whole lot of money. Let’s do two, see how it goes, and let’s focus on getting medicines. That was perfect for us. We didn’t give away a lot of the pipeline, we don’t need to resource like crazy, and yet we learn in large patient populations.”
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 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.
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