At the Protein Engineering Summit (PEGS) and at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in Los Angeles, Orna Therapeutics presented exciting data on their lead program ORN-101, a revolutionary investigational class of engineered circular RNA (oRNA) therapies. ORN-101 is an in situ CAR program in the development stages, which is paving the way for a new era of therapies for the treatment of various diseases.
Orna FoRCE has enabled us to create ORN-101, a powerful anti-cancer circular RNA therapy administered via LNP, and we’ve seen a remarkable 20-fold decrease in the required dosage when compared to earlier versions. This means we can provide multiple doses of our off-the-shelf immunotherapy, providing faster and simpler treatment for more patients. Robert Mabry, PhD, Chief Scientific Officer of Orna, is thrilled with the results.
Synthetic Circular RNA as a New Therapeutic Modality
Orna, a pioneer in the field of mRNA therapeutics, has uncovered an exciting breakthrough: the discovery of novel internal ribosome entry site (IRES) elements that maximize elevated and durable protein expression. This library of IRES elements can be used to drive higher protein expression in the desired cell type targets, providing a more reliable alternative to mRNA therapies.
What’s more, oRNA structure makes it more resistant to rapid degradation, simplifying formulation and manufacture in the lab. With these desirable features, oRNA therapeutics can be developed to treat a range of conditions, from infectious diseases to oncology and genetic disorders.
In situ CAR Therapy Using oRNA
Over the past four years, Orna has revolutionized CAR-T therapies by developing ORN-101 – a therapeutic class that eliminates the need for lymphodepletion, while providing off-the-shelf redosability in an autologous setting. This groundbreaking achievement combines oRNA and a proprietary LNP, and the latest data show ORN-101’s remarkable tumor eradication ability after just 2-3 doses in a mouse model – even at 10-20-fold lower doses than previously reported.
ORN-101 features high expression of the CAR driven by an optimized IRES element, selected by Orna’s FoRCE platform to ensure durable protein expression.
ORN-101, Orna’s groundbreaking program, is an innovative in situ CAR therapy that could revolutionize cancer treatment. By using a proprietary lipid nanoparticle (LNP) to package an oRNA molecule, this therapy could provide reliable dose control and avoid patient lymphodepletion – overcoming the barriers of existing autologous ex vivo CAR-T therapies.
Preclinical data has illustrated its potential to suppress and even eradicate tumors in animal models, suggesting that ORN-101 could be a game-changer in the battle against cancer.
About Orna Therapeutics:
Orna Therapeutics is revolutionizing the field of RNA therapeutics, bringing new possibilities for medical treatment. Their circular RNA (oRNA) is created in a single step through self-circularization of engineered linear RNA, giving it advantages over traditional linear mRNA therapies, such as easier production, enhanced protein expression, encapsulation within lipid nanoparticles (LNPs), and immunoquiescence.
These LNPs, developed by Orna, deliver oRNA to targeted areas of the body, like immune cells. Founded in 2019 by MPM Capital and its affiliate BioImpact Capital, Orna is rooted in groundbreaking research from MIT.