CO has Significant Potential in a Variety of Ischemia-Reperfusion, Fibrotic, and Inflammatory Diseases

Delayed Graft Function (DGF)

There are >17K total kidney transplants per year in the US alone, with nearly half of the 13K cadaveric kidney transplants leading to delayed/slow graft function (DGF/SGF). DGF/SGF significantly increases the risk of acute and chronic organ failure. iCo for DGF would allow for decreased graft failure rates and improved graft function from donors after cardiac death (DCD) and extended criteria donors (ECD). This in turn would shorten transplant list wait times, reduce morbidity/mortality and follow-up dialysis, and reduce overall costs of successful transplants

Patients Receiving Cadaveric Kidneys Each Year, with Risk of DGF
Additional Post-Transplant Costs in First Year with DGF
Five-year Survival Rate for Patients Whose DGF Leads to Acute Rejection

Unmet Medical Need

  • About half of the 13K US cadaveric kidney transplants per year lead to delayed/slow graft function
  • DGF episodes are associated with a significantly increased incidence of acute and chronic transplant rejection (ARE/CRE)
  • An inhaled CO treatment for DGF would allow higher utilization of kidneys from DCD and ECD donors

Health Economic Proposition

  • Studies show patients with DGF have significantly lower graft survival and higher morality rates
  • An Effective Treatment for DGF eliminates years of dialysis costs, saving ESRD and private payors hundreds of thousands of dollars (per patient)
  • A therapy for DGF would significantly increase utilization of marginal kidneys (current discard rate of 40-60%)

iCO for DGF Market Potential

  • There are ~13K cadaveric donor kidney transplants per year in US, ~1.5K per year in Canada, and ~14K per year in the EU – effective treatment of DGF will lead to greater number of transplants performed
  • By reducing DGF, transplant list wait times would be shortened, overall morbidity/mortality would be reduced, and overall cost of transplants would be lowered
  • iCO for DGF could reach $300M+ annual revenues with less than one-third transplant penetration for hospital treatment, and one-third of those moving on to home treatment

Idiopathic Pulmonary Fibrosis (IPF)

IPF is a progressive fibrotic deterioration of lung function with a median survival time of under four years from diagnosis.  Two recently approved medications only moderately slow progression, with significant adverse effects seen in trials, and like most other products in the pipeline involve a similar mechanism of action.  iCO acts via multiple anti-fibrotic, anti-apoptotic, anti-inflammatory and vasodilatory pathways which should show synergy with Ofev®/Esbriet®, the two currently approved and widely prescribed IPF therapies.

Total Patients with IPF in the United States
Years Mean Survival Time from Diagnosis
Estimated Annual Cost of Recently-Approved Medications

Unmet Medical Need

  • Idiopathic Pulmonary Fibrosis: progressive deterioration of lung function and near-universal mortality within five years from onset
  • No known cause, no cure
  • Mean survival time only 3.8 years
  • Two recently approved medications only moderately slow progression, with significant adverse effects seen in trials
  • Most of competitive pipeline targets one mechanism only

Health Economic Proposition

  • Approved medications Ofev® (nintendanib, BI) and Esbriet® (pirfenidone, Roche) priced at nearly $100K/year
  • The only fully effective treatment, a double-lung transplant, costs ~$800K end-to-end
  • CO for IPF offers:
    • Synergy with Ofev/Esbriet for Improved disease progression
    • Lower all-in cost per year, Easier dosing schedule

iCO for IPF Market Potential

  • Prevalence of IPF is >120K in US, >20K in Canada, >150K in Europe, and ~20K in Japan
  • Clinicians estimate 70% of IPF patients are early enough in disease progression to see meaningful clinical improvement from stopping/slowing expansion of fibrosis
  • Even at half or less Ofev pricing, $2B annual revenues could be reached with only 30% patient penetration in only the three markets listed above