Korro and Tevard outlined approaches designed to expand the therapeutic use of RNA medicines beyond protein silencing, highlighting programs that aim to repair genetic defects or restore production of full-length proteins.
Speaking during a Chardan panel on RNA medicines, Ram Aiyar, CEO and president of Korro (NASDAQ:KRRO), described the company’s approach to RNA editing using the endogenous ADAR protein. Korro’s drug product is an oligonucleotide designed to act as a “landing pad” for ADAR, enabling a single RNA base change, he said.
Aiyar said Korro’s focus is not solely on repairing pathogenic variants, but also on using RNA editing to create targeted amino-acid changes that can activate biological pathways. “The real benefit of the technology is going after post-translational modifications, making a change in an amino acid, and giving a biological pathway and activating it,” he said.
Korro Advances Urea Cycle Disorder Program
Korro’s lead program, KRRO-121, targets urea cycle disorders, a group of genetic diseases in which patients are unable to adequately clear ammonia. The therapy is designed to make a single codon change in glutamine synthetase, a liver protein involved in converting ammonia into glutamine.
According to Aiyar, the treatment is intended to transiently stabilize glutamine synthetase, potentially helping patients clear ammonia and blunt ammonia spikes. He said Korro had begun a single-ascending-dose and multiple-ascending-dose clinical study and completed dosing in its first cohort. The company expects to enter patient testing in the first half of the following year and report data in the second half.
Aiyar pointed to genetic evidence and preclinical studies as supporting the program. Korro has evaluated KRRO-121 in multiple preclinical urea cycle disorder models, including OTC mouse models, and reported that the therapy prevented or reduced the ammonia response following ammonium chloride challenge. The company has also shown in monkeys that it can direct cells to make the desired RNA change, he said.
The company views KRRO-121 as a potential treatment across multiple urea cycle disorder mutations, rather than a therapy limited to a specific genetic subtype. Aiyar said Korro hopes to demonstrate not only ammonia reduction, but also improvements that could allow patients to consume more protein or rely less on nitrogen-scavenging treatments.
He characterized the condition as an ultra-rare disease affecting approximately 6,500 patients in the U.S. and said current nitrogen scavengers treat about 800 patients and generate more than $400 million in revenue. Korro estimates a potential $1.5 billion market opportunity for a pan-urea cycle disorder therapy, though that figure reflects the company’s assessment.
Lessons From Alpha-1 Program
Aiyar also discussed Korro’s earlier KRRO-110 program for alpha-1 antitrypsin deficiency, which used a single-stranded oligonucleotide delivered in a lipid nanoparticle. The program produced repaired protein in every treated individual, he said, but the company identified stability issues in patients that were not seen in healthy volunteers.
Korro chose not to continue investing in that first-generation product and instead shifted resources to a second-generation candidate using a conjugate delivery approach designed for subcutaneous administration rather than intravenous lipid-nanoparticle delivery.
The company has reported more than 90% to 95% editing in animal models with the newer candidate, according to Aiyar. He said Korro expects to provide guidance soon on when the program will enter the clinic and when data could be expected.
Tevard Targets Nonsense Mutations With Engineered tRNA
Elisabeth Gardiner, chief scientific officer and president of Tevard, described the company’s engineered transfer RNA, or tRNA, platform. Tevard is developing suppressor tRNAs intended to recognize nonsense mutations, deliver the appropriate amino acid, and enable production of full-length protein.
Gardiner said nonsense mutations affect approximately 35 million people. The approach could be particularly relevant for large structural proteins, such as dystrophin, titin, lamin A and filamin C, which can be difficult to deliver in full using conventional adeno-associated virus, or AAV, gene therapy.
Rather than delivering a full protein, Tevard delivers DNA encoding the suppressor tRNA. Gardiner said the small cargo is portable and can potentially be used with lipid nanoparticles, AAVs, and other delivery systems. The company has focused on creating a tRNA cassette that can be inserted into multiple delivery vehicles.
In preclinical work, Tevard has observed full-length rescue of dystrophin and titin in several animal models, Gardiner said. The company has also tested suppressor tRNAs in several AAV settings in monkeys, where she said they appeared safe and well tolerated.
- Tevard reported that its engineered tRNAs showed activity even when representing about 1% of the total cellular tRNA pool.
- In a challenging animal model, the company observed a 50% reduction in creatine kinase within 12 weeks, according to Gardiner.
- Tevard is conducting ribosome profiling and proteomic work to assess whether corrected proteins function normally.
Gardiner said Tevard is developing trial designs for Duchenne muscular dystrophy and a titin-related dilated cardiomyopathy program. She said the company hopes to enter the clinic by the end of 2027 or the beginning of 2028, while noting that the timeline was conservative and could move faster.
Discussing another tRNA-focused company, Alltrna, Gardiner said the companies’ approaches are complementary. She said Alltrna is primarily focused on TGA stop codons, lipid-nanoparticle delivery and liver-related inborn errors of metabolism, while Tevard is pursuing a different delivery and disease-focus strategy.
About CAMP4 Therapeutics (NASDAQ:CAMP)
CAMP4 Therapeutics Corporation is a clinical-stage biotechnology company focused on developing RNA-based medicines for genetic diseases caused by insufficient production of essential proteins. The company’s approach is designed to increase expression of a patient’s existing genes rather than replace or edit them.
CAMP4 uses its RegRNA platform to identify regulatory elements in messenger RNA and develop RNA activators, including small activating RNAs, that may stimulate production of targeted proteins.
