RGN-352

RegeneRx is developing RGN-352, an injectable Tβ4 formulation for the treatment of cardiac damage post-acute myocardial infarction (MI) and for the treatment of chronic heart failure, as well as for various nervous system pathologies. Numerous animal models of cardiac injury have shown the effectiveness of RGN-352 in reducing scar volume, in increasing cardiac function, and in survival. Preclinical studies have identified Tβ4’s ability to recruit stem cells and stimulate differentiation, reduce apoptosis and inflammation, protect cells from cytotoxicity, increase angiogenesis and reduce scar formation in animal models.

Recent animal data have also shown the restorative potential of RGN-352 in the treatment of certain central nervous system disorders, such as stroke, traumatic brain injury (TBI), and peripheral diabetic neuropathy.

CARDIOVASCULAR DISORDERS

The following observations of Tβ4’s effects on myocardial infarction and chronic heart failure in a variety of animal models have been published in major high-impact scientific journals and underlie the rationale for evaluating RGN-352 in MI and heart failure patients:

  1. Tβ4 reduces scar size after an myocardial infarction – Nature 2004
  2. Tβ4-Induced cardioprotection is associated with activation of "survival" kinases – Nature 2004
  3. Tβ4 reduces infarct size and improves cardiac function – Nature 2004
  4. Tβ4 reduces infarct size and improves post-ischemic function in the porcine model – Circulation 2008
  5. Tβ4 decreases apoptosis in infarcted hearts – Journal of Molecular and Cellular Cardiology 2012
  6. Tβ4 enhances fetal gene expression after myocardial infarction – Nature 2011
  7. Tβ4 promotes angiogenesis in infarcted myocardium – Journal of Molecular Cell Cardiology 2009
  8. Tβ4 induces Epicardium progenitor cell migration into injured tissue and transformation to cardiomyocytes – Nature2011
  9. Tβ4 promotes reprogramming of fibroblasts – Nature 2012

CNS AND PNS DISORDERS

Preclinical data support potent regenerative/protective effects and dose responses of Tβ4 on the peripheral and central nervous systems. For reasons listed above, Tβ4 has significant potential for the treatment of various neurological injuries such as traumatic brain injury, stroke, peripheral neuropathy, multiple sclerosis, spinal cord injury, etc. As with myocardial studies, Tβ4 has been shown to promote tissue repair/regeneration in numerous CNS and PNS animal models:  

Traumatic brain injury

  • Increased spacial learning and sensorimotor functional recovery
  • Decreased lesion volume and hippocampal cell loss
  • Increased angiogenesis, cell proliferation, neurogenesis, axonal remodeling

Stroke

  • Increased myelinated axons, myelinating oligodendrocytes, remyelination 
  • ncreased progenitor cells and vessel density

Peripheral neuropathy

  • Increased neurological function and nerve function
  • Increased vascular density and blood flow
  • Increased angiopoietin-1

Spinal cord injury

  • Decreased scar size and inflammation
  • Increase in myelin basic protein
  • Increased surviving neurons and oligodendrocytes
  • Improved behavioral assessments

Multiple Sclerosis

  • OPC’s increased by >200% in brain SVZ and >80% in white matter
  • Mature oligodendrocyte cells increased 90% in white matter
  • Neurological relative functional recovery 50% greater in Tβ4 treatment group
  • Oligodendrogenesis increased in brain by approximately 100%
  • Inflammatory infiltrates adjacent to vessels in brain reduced by 30%

PHASE I

RegeneRx successfully completed a Phase 1 clinical trial in 80 healthy subjects using an acute dosing regimen. RGN-352 was shown to be safe and well-tolerated at 4 dose levels. RegeneRx has also successfully completed a $3 million grant from the National Heart, Lung, and Blood Institute of the NIH to conduct a number of additional animal toxicology and pharmacokinetics studies to support human clinical trials.

To date, over 650 patients have been tested with RegeneRx’s Tβ4-based product formulations administered topically to the skin, the eye, and injected into the blood stream. The formulations have produced no serious adverse events and have been deemed to be safe and well-tolerated in every clinical study to date. We believe RGN-352 is now ready for Phase 2 clinical trials in the acute setting.


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