ORN-101, an optimized development-stage in situ CAR program, shows tumor eradication in a mouse model at doses far lower than previously reported results

Orna’s FoRCE screening platform has enabled the identification of oRNAs that drive high protein expression, creating broad value across all of Orna’s programs

CAMBRIDGE, MA, USA I May 18, 2023 I Orna Therapeutics, a biotechnology company pioneering a new investigational class of engineered circular RNA (oRNA) therapies, presented data on the progress of lead program ORN-101, a development-stage in situ CAR program, at the Protein Engineering Summit (PEGS) and at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in Los Angeles.

The presentations include a session and talk at PEGS, as well as a poster presentation at ASGCT, which may be viewed on the Orna website here.

“Using the Orna FoRCE platform, we’ve been able to develop ORN-101, a potent anti-cancer circular RNA therapy delivered via LNP,” said Robert Mabry, PhD, Chief Scientific Officer at Orna. “We have achieved 20-fold lower dosing in animal models compared to earlier versions of the product, allowing us the flexibility to administer multiple doses of our off-the-shelf immunotherapy – something that could allow us to treat more patients quickly and easily.” 

Synthetic Circular RNA as a New Therapeutic Modality
Elevated and durable protein expression – two features where mRNA falls short – are maximized with circular RNA in part due to Orna’s discovery of novel internal ribosome entry site (IRES) elements necessary for translation. Compared to previously known IRES elements, Orna’s library of IRES elements can be used to drive higher protein expression in desired cell type targets. oRNA, because of its shape, is more resistant to quick degradation in the body, is easier to manufacture and formulate in the lab, and is immunoquiescent. These desirable features further allow oRNA therapeutics to be developed for applications beyond infectious disease, including oncology and genetic disorders.

In situ CAR Therapy Using oRNA
Over the past four years, Orna has worked to develop a therapeutic class capable of delivering a chimeric antigen receptor (CAR) to immune cells within a patient, eliminating the need for lymphodepletion typically required for engineered cell therapies, while providing off-the-shelf redosability in an autologous setting. ORN-101 combines oRNA and a proprietary LNP, and these latest data show ORN-101’s tumor eradication ability after 2-3 doses in a mouse model, effective at 10-20-fold lower doses than Orna has previously reported. ORN-101 features high expression of the CAR driven by an optimized IRES element, selected by Orna’s FoRCE platform to yield durable protein expression.

About ORN-101:

ORN-101, Orna’s lead program, is a development-stage in situ CAR therapy designed to modify a patient’s immune cells inside their body. Comprising an oRNA molecule packaged inside a proprietary lipid nanoparticle (LNP) formulation, this easily redosable format could avoid patient lymphodepletion and allow for reliable dose control, overcoming barriers of existing autologous ex vivo CAR-T therapies without sacrificing efficacy. Preclinical data demonstrates tumor suppression and eradication in animal models, suggesting the possibility that oRNA-LNP based cancer therapies could disrupt traditional CAR-T cellular therapies.

About Orna Therapeutics:

Orna Therapeutics is reshaping RNA therapeutics to open a new world of treatment possibilities. Orna’s circular RNA (oRNA) is created in one step by self-circularization of an engineered linear RNA. In this form, oRNA enjoys unmatched advantages over traditional linear mRNA therapies including simplified production, increased protein expression, easier encapsulation into lipid nanoparticles (LNPs), and immunoquiescence. Orna’s proprietary LNPs deliver the oRNA to specific areas of the body, such as immune cells. Founded in 2019 based on groundbreaking research from MIT, Orna was built by MPM Capital and its affiliate BioImpact Capital. To learn more visit: www.ornatx.com and follow us on Twitter and LinkedIn

SOURCE: Orna Therapeutics