October 6-9, 2024, Montreal, Canada, Rona Therapeutics presented pioneering extrahepatic small interfering RNA (siRNA) delivery data to the Central Nervous System (CNS) at the 20th Annual Meeting of the Oligonucleotide Therapeutics Society(OTS).

APOLLO is Rona Therapeutics extrahepatic platform utilizing ligand siRNA bioconjugates to achieve tissue specific delivery. With a novel receptor-targeting conjugated siRNA, up to 87% knockdown of target protein is achieved across various CNS areas in non-human primates (NHP) with intrathecal (IT) administration. The ligand siRNA conjugate has also demonstrated durable target silencing and favorable safety profile.

In addition to the proprietary extrahepatic delivery for CNS, Rona Therapeutics has also achieved significant advancements in the design and synthesis of the siRNA. Based on the structural insight into molecular mechanism of siRNA, Rona Therapeutics designed and synthesized a novel C4′, C5′ cyclobutene-fused spirocyclic phosphonate nucleotide, known as cis-SCP. Besides the stability improvement provided by the C-P bond, the AGO2-well-fit rigidity of this novel structure may further enhance potency in RNAi, compared to structure-rotatable 5′-phosphate mimics in this space.

As one of the highest unmet medical needs and greatest therapeutic challenges, multiple CNS diseases have been associated with dominant gain-of-function mutations. RNA interference could block the expression of these disease-causing genes and provide a targeted and controllable therapy for these patients. Rona Therapeutics' Central Nervous Delivery Platform facilitates selective delivery of therapeutic siRNAs to the spinal cord and multiple brain regions via a receptor-targeting small molecule, showcasing the broad distribution and potent knockdown across brain regions in all tested species (mice, rats, and non-human primates).

Furthermore, the company presented a novel siRNA backbone modification with best-in-class potency in preclinical studies - a chemistry strategy to improve the druggability of siRNAs. This breakthrough in siRNA design and synthesis, combined with the innovative delivery method, holds promise for more effective and efficient treatment options in the CNS and beyond.

Rona Therapeutics' exploration and research and development efforts have positioned them at the forefront of global research in this field including demonstrate Rona Therapeutics' expertise in developing innovative siRNA delivery systems and their advanced understanding of receptor-mediated endocytosis. This remarkable disclosure has garnered widespread attention from both academic and industry, fostering interest and anticipation in the potential of this new delivery method within the pharmaceutical sector. Rona Therapeutics' pioneering research continues to pave the way for advancements in oligonucleotide therapeutics, offering new hope for patients with various neurological disorders.

About Rona Therapeutics

Rona Therapeutics is a global leader in nucleic acid innovative drug platform company, specializing in the treatment of metabolic diseases and CNS degenerative diseases. Rona Therapeutics is always committed to developing the best and first-in-class siRNA drugs and has unique differentiation and innovation in its liver-targeted metabolism-related pipeline products in cardiovascular diseases, MASH, obesity, and kidney diseases. In addition, Rona Therapeutics is focusing on the potential of extra-hepatic nucleic acid delivery in CNS degenerative diseases and has successfully established a proprietary extra-hepatic delivery platform to treat a range of complex diseases, such as ALS, Alzheimer's disease, etc. which are difficult to treat with traditional drug therapies.