Targeting the SLIT3 Pathway to Promote Bone Formation

Background & Unmet Need

• One in two women and one in four men experience a fracture due to osteoporosis in their lifetime
• However, the application of currently available therapeutic methods is limited by either the side effects or by the maximum therapy duration
• Biophosphonates are the most widely prescribed but are associated with nausea, abdominal pain and heartburn-like symptoms
• Denosumab produces similar or better bone density results but is associated with rare but serious side effects
• Bone-building medications such as teriparatide and romosozumab may be used in patients who fail or are intolerant to other therapies
• Unmet Need: Methods to prevent and reverse osteoporosis that act through novel mechanisms

Technology Overview

• The Technology: Novel methods that involves targeted administration of osteoanabolic agents to promote bone formation, boost bone strength, and enhance bone healing
• Discovery: Slit guidance ligand 3 (SLIT3) is a potent proangiogenic factor that enhances bone fracture healing and counteracts bone loss
• PoC Data: In a mouse model of osteoporosis, SLIT3 had comparable efficacy to PTH-based anabolic agents
• Local therapeutic delivery was achieved using a SLIT3-loaded collagen sponge, which limits potential for extra-skeletal toxicities
• SLIT3 provides a complementary pathway to PTH-based agents, suggesting they may be used sequentially or in combination to enhance efficacy

Technology Applications

• Treatment and prevention of bone loss (osteoporosis)
• Promotion of bone healing and strength
• Use with a range of orthopedic procedures to enhance healing or osteointegration
• Inhibition of SLIT3 may prevent unwanted bone formation

Technology Advantages

• Distinct mechanism of action from approved therapies
• May be used sequentially or in combination with PTH-based anabolic agents
• Local drug delivery minimized extra-skeletal toxicities
• Can be delivered in combination with a carrier or medical device