Dendrimers are tree-like hyperbranched polymers (~ 4 nm in diameter), with a well-defined structure. The surface of the dendrimer has many functional groups that can be tailored to attach drugs. The hydroxyl poly(amidoamine) dendrimers (PAMAM) used in this platform technology rapidly distribute throughout the body after IV dosing, do not bind to proteins or tissues, are non-toxic in animals at high IV doses (1000 mg/kg), and are excreted intact through the urine. Each dendrimer-drug conjugate is a new chemical entity (NCE).

The co-founders of our company discovered that these dendrimers target activated microglia in the neuroinflammatory regions of the brain. OP-101 is a hydroxyl dendrimer linked through a disulfide bond to an anti-inflammatory drug, which delivers drug selectively to activated microglia for improved efficacy and reduced side effects.

How Does This Technology Work?



Single Dose of OP-101 Reduces Neuroinflammation in Rabbit Model of Neonatal Brain Injury (NBI)

  • Untreated rabbits have severe motor function impairment and most die within 10 days.
  • Rabbits with NBI , when treated with a single dose of OP-101, have a dramatic improvement in motor function by 5 days
  • OP-101 treated rabbits mature to adulthood without significant signs of neurological damage
  • OP-101 selectively targets injured microglia and releases anti-inflammatory drug inside the cells
  • OP-101 leads to decreased oxidative injury and neuroinflammation enabling normal brain development.
  • More study details:

These dendrimers have been shown to target neuroinflammation in the brain and the retina in multiple mouse, rat, rabbit, canine and primate models. Of direct relevance to Orpheris, a single intravenous dose of OP-101, administered after birth, for a brain injury created before birth, led to a dramatic improvement in motor function by 5 days, in a clinically relevant rabbit model of NBI. OP-101 was superior to free drug, and produced improvements that could not be achieved with a 10-fold higher dose of free drug.

Ashvattha Therapeutics LLC, owns the rights to an umbrella of patents that cover the targeted hydroxyl dendrimer platform including composition of matter for OP-101 and other compounds. Orpheris has licensed these patents for up to 3 products with an initial focus on orphan diseases. The technology is protected through issued and pending patents that provide coverage until 2034.