Fibrosis unmet clinical need
What is Fibrosis?
  • Fibrosis is a hallmark of many major illnesses including heart failure, chronic liver diseases, pulmonary fibrosis, and many cancers
  • Fibrosis is a scarring process resulting in increased extracellular matrix production, chiefly type I collagen
  • The presence of fibrosis can be diagnostic, e.g. for non-alcoholic steatohepatitis (NASH)
  • The extent of fibrosis is prognostic and a good indicator of disease progression or treatment efficacy 

Why Imaging?
  • Diagnosis, prognosis, and therapy monitoring
  • Gold standard for assessment of fibrosis is biopsy
  • Biopsy is invasive, carries real risks of morbidity and mortality, and typically cannot be performed repeatedly
  • Alternate methods for assessing fibrosis suffer from poor sensitivity or specificity for disease and are of little use for disease staging
  • Better tools are urgently needed for diagnosis, staging, and monitoring of therapy

Collagen Medical Solution

Approach
  • Excess collagen can be imaged using a targeted small molecule MRI probe
  • Broad utility across different diseases and organ systems
  • MRI provides high spatial resolution and ability to quantify fibrosis locally and throughout the entire organ (unlike blood tests)
  • No ionizing radiation (unlike PET, SPECT), and does not raise concerns of radiation burden in following disease progression in relatively healthy subjects on an annual/semi-annual basis
Technology

  • Short peptides specific to type I collagen
  • Optimized affinity, metabolic stability, and functionalization to enable imaging
  • Lead probe CM-50 is high affinity, high avidity collagen binding peptide that is conjugated to three gadolinium (Gd) chelates for strong, positive MR signal enhancement
  • Probes localize and are retained in areas of increased collagen deposition, resulting in a prolonged and selective enhancement of collagen rich tissue in an MRI scan thereby rendering a quantitative assessment of the extent of diseas
  • Probes are relatively small (<5 kDa), renally excreted, and show no non-specific binding
  • Additional expertise in MR acquisition and quantitative methods for fibrosis detection and disease staging

Indications and Preclinical Efficacy

Liver Fibrosis

  • Present in hepatitis C and B (HCV, HBV), alcoholic liver disease and nonalcoholic steatohepatitis (NASH)
  • HCV affects 2% of the US population and accounts for the majority of liver transplants
  • 8.5% of the population abuse or are dependent on alcohol and are at high risk for alcoholic liver disease
  • Nonalcoholic fatty liver disease (NAFLD) is epidemic (driven by the rise in obesity, diabetes) with 17 – 33% of the US population afflicted.
  • 30-50% of NAFLD patients will progress to (NASH), and this group is further at risk for progression to cirrhosis (15-25%), organ failure, liver cancer or death

Collagen probe CM-50 can detect and stage liver fibrosis in rodent models of disease




Myocardial Fibrosis

  • Fibrosis is a key marker of adverse cardiac remodeling
  • Strong correlation between the extent of fibrosis and the progression of congestive heart failure
  • Diffuse fibrosis can lead to atrial arrhythmia (2.2 M patients) and ventricular arrhythmia (cause of 350,000 death/year)
  • Myocardial fibrosis imaging test would serve a market of >4M patients with heart arrhythmia, 5.8M in heart failure, in addition to patients with ischemic heart disease, hypertropic cardiomyopathy and dilated cardiomyopathie
CM-50 can detect and quantify extent of myocardial fibrosis in mouse model




Pulmonary Fibrosis

  • Idiopathic pulmonary fibrosis and other fibrotic diseases of the lung
  • Replacement of normal lung with scar tissue causes irreversible decrease in oxygen diffusion capability
  • Increased risk for pulmonary infection, pulmonary hypertension, heart failure
  • 50,000 new cases diagnosed each year in the US, up to 40,000 deaths/year
CM-50 specifically identifies pulmonary fibrosis in mouse model of disease