Orna Therapeutics Announces First-in-Class, Breakthrough Data Demonstrating Potential of Circular RNA Platform at ASGCT 2022

Advances in oRNA expression and delivery enable pipeline of therapeutics across a diverse
range of disease areas

Lead isCAR program shows possibility of tumor eradication in preclinical animal models with
promise of translation to non-human primates and patients

CAMBRIDGE, Mass., May 16, 2022 /PRNewswire/ -- Orna Therapeutics, a biotechnology company pioneering a new class of fully engineered circular RNA (oRNA) therapies, today for the first time announces data from its lead isCAR program that validates the potential of the company's novel oRNA technology and LNP delivery platform. Based on advances in the expression of oRNA as well as its delivery to immune cells, Orna has demonstrated tumor suppression and eradication in an animal model pointing to the possibility that oRNA-LNP based cancer therapies could eventually overtake cell therapies.

Additional data to be presented demonstrate the utility of Orna's proprietary FoRCE screening platform which has enabled the company to discover and characterize a major new resource for protein expression based on internal ribosome entry sites (IRESs). Orna will also present data showing the development of novel immunotropic lipid nanoparticles (LNPs), and the potential of oRNA in genetic muscle disease and vaccines. View full presentations from ASGCT on our website here.

"At Orna, we've created the world's leading circular RNA company and are building a platform and pipeline with the potential to change the way we treat disease," said Tom Barnes, PhD, Orna's Chief Executive Officer and oral presenter at ASGCT. "Presented for the first time, these data suggest our oRNA technology and LNP delivery favorably combine to maximize our reach into multiple therapeutic areas – validating our expanded pipeline beyond cancer to include muscle genetic diseases and vaccines."

isCAR: Revolutionizing CAR-T Cell Therapy with the Possibility of Eradicating Tumors
Our lead program is an in situ CAR therapy that combines oRNA and custom engineered LNPs to create modified immune cells within the patient. This easily redosable format would not require patient lymphodepletion and would allow for reliable dose control, overcoming barriers of ex vivo CAR-T therapies. Data being presented demonstrate that oRNA-LNP can eradicate cancer cells in an animal model. Additional iterative data in rodents and non-human primates gives Orna confidence that this may successfully translate into humans.

"We are excited about the preclinical results in our lead isCAR program as we clearly see the opportunity to overcome significant hurdles in current ex vivo approaches, suggesting that oRNA-LNP based cancer therapies may eventually overtake cell therapies," said Robert Mabry, PhD and Chief Scientific Officer at Orna. "We believe that data from iterative animal studies can support our plans to deliver in situ CAR-T therapies to the clinic."

FoRCE: Formulated oRNA Cell-based Evaluation Platform
Orna is also presenting new data from our proprietary FoRCE screening platform, which captures the entire oRNA production, formulation, and evaluation process in an arrayed and automated format. In a first application, Orna has screened and characterized thousands of IRES elements in multiple primary human cell types. IRES identification and development is critical for optimizing oRNA function via tunable protein expression. Orna has discovered many novel IRES elements that drive oRNA expression to levels well above those of standard IRES elements, including some that show differential activity across cell types. These results open a new technological toolkit for driving protein expression from circular RNA.

Breadth of Platform
Orna has extended its oRNA-LNP technology into several other indications including Duchenne Muscular Dystrophy and vaccines and believes there are many additional opportunities this technology can bring to existing therapeutics.

Duchenne Muscular Dystrophy (DMD):
Orna will present data highlighting the ease of working with very large oRNAs. Data demonstrate, for the first time, non-viral delivery of a large, full-length, dystrophin-encoding RNA in human cells, as well as in vivo delivery of smaller length versions in mouse models. These data are an encouraging first step on the path to delivering full-length gene therapy to patients with DMD.

Vaccines:
Orna is investigating the suitability of oRNA combined with intramuscularly administered immunotropic LNPs for vaccine applications, including for COVID-19. The oRNA half-life observed in muscle and immune cells, combined with the intramuscular administration of immunotropic lipids, suggests that oRNA-LNP technology may be beneficially applied to vaccine development.

Conference presentation details are shared below.

Oral Presentations:
In situ CAR Therapy Using oRNA Lipid Nanoparticles Regresses Tumors in Mice
Presenter: Tom Barnes, Ph.D., CEO
Date/Time/Location: Monday, May 16, 2022 from 9:10 - 9:45 a.m. ET in Room 207
Session: Scientific Symposium: Function and Therapeutics Applications of Circular RNAs (circRNAs)

Discovery of Translation Initiation Elements Enabled by a Parallel Arrayed Screen of Full-length Viral UTRs in Synthetic Circular RNA
Presenter: Alexander Wesselhoeft, Ph.D., Director, Molecular Biology
Date/Time/Location: Monday, May 16, 2022 from 11:30 – 11:45 a.m. ET in Salon H
Session: Oral Abstract Session: Oligonucleotide Therapeutics

Poster Presentations:
Improved Immune Cell Expression with Circular RNA (oRNA) in vivo
Presenter: Kevin Kauffman, Ph.D., Principal Scientist
Date/Time/Location: Monday, May 16, 2022 at 5:30 p.m. ET in Hall D
Session: Poster Session: Oligonucleotide Therapeutics I

Systemic Delivery of Circular RNA Encoding Partial Dystrophins and Expression in Skeletal Muscle
Presenter: Tatiana Fontelonga, Ph.D., Scientist
Date/Time/Location: Tuesday, May 17, 2022 at 5:30 p.m. ET in Hall D
Session: Poster Session: Oligonucleotide Therapeutics II

About Orna Therapeutics
Orna Therapeutics is a biotechnology company pioneering a new class of fully engineered circular RNA (oRNA) therapeutics with the potential to change the way we treat disease. Orna's proprietary platform combines novel technology to design circular RNA transcripts that drive protein expression with validated and unique LNP delivery solutions. Optimized oRNA-LNPs offer simplified production, improved formulatability, and superior protein expression over traditional mRNA approaches. The combined advantage of these two technologies puts Orna ahead of the curve and expands the possibilities of what RNA therapeutics can achieve.  To learn more visit: www.ornatx.com and follow Orna Therapeutics on Twitter and LinkedIn.

SOURCE Orna Therapeutics