Pipeline – DEMO
Our strategy
Korro Bio is focused on diseases where our platform, OPERA®, can provide a unique solution. We are targeting disease-causing sequences that would be responsive to the safe and targeted editing of RNA. Our current focus areas include the liver and central nervous system.
Alpha-1 antitrypsin deficiency
Repairing a pathogenic variant
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We are developing KRRO-110 as a potential differentiated and disease-modifying treatment for alpha-1 antitrypsin deficiency (AATD).
AATD is caused by mutations in the SERPINA1 gene, the most common of which, called the “Z” mutation, or “G” to “A” mutation, changes a guanosine to an adenosine. This mutation on DNA gives rise to mutated messenger RNA, or mRNA, which in turn produces an abnormal AAT protein.
Most of this abnormal protein aggregates and gets trapped in the liver, which can lead to cirrhosis and other debilitating liver complications in some patients.
KRRO-110 is a proprietary RNA editing oligonucleotide that is delivered to liver cells using a validated lipid nanoparticle (LNP) delivery system. Once inside these cells, KRRO-110 harnesses the naturally occurring ADAR editing system to repair the mutation that causes AATD and restore normal levels of AAT protein. This approach has the potential to provide clinically differentiated benefits for both liver and lung manifestations of the disease.
Parkinson’s disease
Repairing a pathogenic variant
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We are developing proprietary oligonucleotides that address the leucine-rich repeat kinase 2 (LRRK2) mutation for Parkinson’s disease (PD). PD is a complex and progressive disease that results, in part, from the loss of neurons essential for controlling body movement. Mutations in LRRK2 are the most common genetic cause of PD, and increasing evidence supports a role of LRRK2 in idiopathic PD as well.
Amyotrophic lateral sclerosis
De novo protein to disrupt aggregation
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We are developing proprietary oligonucleotides targeting the mRNA for TAR DNA binding protein 43 (TDP-43), which is associated with the development of amyotrophic lateral sclerosis (ALS).
ALS is an adult-onset, progressive, and fatal neurodegenerative disorder that causes muscle weakness, paralysis, and ultimately death. The majority of ALS patients die from respiratory failure within three to five years after symptom onset, with a small percentage surviving beyond 10 years. Despite being classified as a rare disease by the FDA and EMA, ALS is considered one of the more common neurodegenerative diseases worldwide.
Subset of pain
De novo protein to modulate currents
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We are developing proprietary oligonucleotides that selectively modulate ion channels associated with pain.
Pain is a condition experienced by millions of patients and is often a component of both rare and common diseases. Despite its prevalence, there remains a significant unmet need for safe and effective pain management, particularly non-opioid therapeutics. While several classes of drugs, including local anesthetics, act as ion channel blockers, they lack specificity and do not selectively inhibit channels associated with pain transmission. Our oligonucleotides are designed to selectively block NaV1.7, an ion channel widely implicated in chronic pain. This targeted approach aims to provide more effective and safer pain management options.
Proposed clinical study of KRRO-10 for AATD
Phase 1/2a, Two Part, Single-led Multiple-Dose Escalation Study
Two clinical study sites identified in Australia with plans to expand into additional sites in Australia and other geographies
Study Population
- Up to 64 adult participants
- PiMM healthy volunteers or clinically stable PiZZ patients
Study Design
- Part 1(SAD): Active: PBO (2:1) Cohorts of PiMM and PiZZ
- Part 2(MAD): Open-label PBO (2:1) Cohorts of PiZZ patients
Endpoints
- Primary: Safety and tolerability
- Secondary: Pharmacokinetic (PK) parameters; T-AAT, M-AAT, Z-AAT, functional antiprotease activity
Clinicaltrials.gov | NCT06677307
