Orna Therapeutics presented compelling new preclinical data for its in vivo CAR therapy approach targeting autoimmune diseases at the 28th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in New Orleans. The data showcased the potential of the company's circular RNA (oRNA®) technology and lipid nanoparticle (LNP) delivery system to revolutionize treatment approaches for autoimmune conditions.
Joseph Bolen, Ph.D., Chief Executive Officer of Orna Therapeutics, emphasized the significance of these findings: "Our CD19 panCAR program has demonstrated not only successful delivery of our lead panCAR LNP to disease-relevant immune cell types, but also robust and sustained B cell depletion at low doses in both peripheral blood and lymphoid tissues in non-human primates."
The presentation, delivered by Megan Hoban, Ph.D., panCAR Program Lead at Orna Therapeutics, highlighted several breakthrough achievements in the company's preclinical research program.
Novel Delivery System Achieves Targeted Immune Cell Penetration
A key challenge in developing effective in vivo CAR therapies has been delivering genetic material to the appropriate immune cells. Orna's approach has validated extra-hepatic delivery to disease-relevant immune cell types, including T cells, in both mice and non-human primates (NHPs) without requiring targeting ligands.
The company's lead panCAR LNP achieved over 60% delivery to peripheral blood and splenic T cells in NHPs, representing a significant advancement in delivery technology. This high efficiency could potentially translate to lower required doses and reduced side effects in clinical applications.
Robust B Cell Depletion at Low Doses
The preclinical data demonstrated that CD19 panCAR doses as low as 0.03 mg per kilogram led to robust B cell depletion, with multi-dosing achieving increased B cell depletion in humanized mice. This suggests that the therapy could be effective at relatively low doses, potentially improving its safety profile.
In non-human primates, the CD19 panCAR induced complete depletion of B cells across peripheral blood, spleen, lymph nodes, and bone marrow. The data showed that peripheral B cells began to reconstitute after three weeks, indicating that the treatment effect is potent but not permanently depleting.
Superior Performance in Lupus Model
Particularly promising results emerged from a humanized lupus mouse model, where CD19 panCAR showed strong B cell depletion and a meaningful reduction in double-stranded DNA (dsDNA) antibody titers compared to rituximab, a standard B cell-depleting therapy currently used for various autoimmune conditions.
This differentiated performance against an established therapy suggests that Orna's approach could potentially offer superior efficacy for patients with autoimmune diseases like lupus, where current treatments often provide inadequate disease control.
Circular RNA Technology Offers Advantages
Orna's proprietary circular RNA (oRNA®) technology forms the foundation of its therapeutic approach. According to the company, oRNA transcripts offer several advantages over traditional messenger RNA (mRNA) approaches, including simplified production, improved formulation into lipid nanoparticles, and superior protein expression.
These characteristics could translate to more efficient manufacturing processes and potentially more effective therapies compared to linear RNA-based approaches.
Path to Clinical Development
Based on these encouraging preclinical results, Orna Therapeutics plans to advance its CD19 panCAR program toward clinical trials in 2026. The company is positioned to potentially transform treatment paradigms for autoimmune diseases, which affect millions of patients worldwide and often lack highly effective therapies with favorable safety profiles.
"These compelling results continue to reinforce our commitment to translating our promising science into meaningful therapies for patients," said Dr. Bolen.
The company's approach could potentially address limitations of current autoimmune disease treatments, which often involve broad immunosuppression with associated infection risks or require regular intravenous administration in clinical settings.
Broader Platform Potential
While the current focus is on autoimmune applications, Orna is developing a proprietary pipeline of in vivo therapies across both autoimmune and oncology indications. The versatility of the platform suggests potential applications across multiple disease areas where targeted immune cell modulation could provide therapeutic benefit.
The company's industry-leading LNP-based delivery systems, comprehensive editing programs, and partnerships with pharmaceutical companies position Orna to advance novel RNA medicines with potential to transform patient care in areas of significant unmet medical need.
