Navega Therapeutics, Inc.

Reformulating NT-Z001 and Its Delivery Route to Treat Rheumatoid Arthritis - Project Absract a Significant Proportion of Rheumatoid Arthritis (RA) PATIENTS—30-70%—CONTINUE to Report Pain Despite Treatment With Disease-modifying Antirheumatic Drugs (dmards). This Persistent Pain May Be Attributed to Incomplete Inflammation Control, Post-inflammatory or Neuropathic Conditions, or Mechanisms Such as Central Sensitization. the Objective of This Sbir Transition Grant Is to Reformulate NT-Z001, an Epigenetic Gene Therapy, to Better Address the Needs of Ra Patients by Enabling Localized Joint Injections Instead of the More Invasive Intrathecal (IT) Route. NT-Z001 Targets the NAV1.7 Sodium Channel, a Key Mediator of Pain, Offering a Novel Approach to Chronic Pain Management That Could Reduce Reliance on Opioids and Other Analgesics. by Downregulating NAV1.7 Expression Through Ai-designed Zinc Finger (ZF) Proteins Fused to a Repressor Domain, NT-Z001 Aims to Provide Durable Pain Relief and Address Inflammation, Macrophage Infiltration, Nerve Sprouting, and Joint Remodeling in Ra. NT-Z001'S Mechanism of Action Directly Interferes With the Pain Transmission Process, Offering a Targeted Alternative That Could Significantly Improve Patient Quality of Life. Preliminary Studies Have Demonstrated NT-Z001'S Ability to Alleviate Pain and Inflammation in Preclinical Models Mimicking Ra Pathology. These Studies Highlight NT-Z001'S Potential to Modulate Pain and Inflammatory Pathways and, Importantly, to Reduce Peripheral Nerve Sprouting, Which Contributes to Chronic Pain in Ra. This Proposal Outlines a Plan to Reformulate NT-Z001 for Intra-articular Delivery, Evaluating Viral (aav and HSV) Approaches to Ensure Effective Localization in the Dorsal Root Ganglia (DRG) After Joint Injections. the Best-performing Formulation Will Be Tested in the Collagen-induced Arthritis (CIA) Model of Ra, Assessing Its Impact on Mechanical Allodynia, Inflammation, and Joint Pathology. If Successful, This Work Will Enhance NT-Z001'S Therapeutic Potential by Offering Ra Patients a Less Invasive and More Effective Option for Pain Management. Additionally, It Could Open the Door to Developing Therapies for Other Chronic Pain Conditions Where Intrathecal Administration Is Not a Suitable Approach.