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Maximizing the Value of Your Assets: Repurposing Compounds to Treat Respiratory Diseases

The discovery and development process averages 13-15 years, and costs as much as $3 billion USD. By comparison, estimates for repurposing known compounds suggest that reprofiling a known compound will take about 6.5 years and the costs are orders of magnitude lower, coming in at $300 million USD1. With emerging access to large pharmaceutical company compounds, there is a golden opportunity to investigate novel treatments and potentially improve the efficiency of pharmaceutical R&D.

Our teams have conducted multiple reprofiling and repurposing studies to help our clients maximize the value of their assets and deliver novel candidates:

  • Oral drugs to inhaled delivery candidates
    • A non-respiratory oral project with known systemic liabilities
    • Compound bank assessed and in vivo proof of concept undertaken via the inhaled route
    • Chemistry optimized to deliver a compound with appropriate duration of action in the lung which entered clinical development for the treatment of asthma
  • Topical (skin) drugs to inhaled delivery candidates
    • A non-respiratory-focused dermal project with known systemic liabilities
    • Compound bank assessed and in vivo proof of concept undertaken via the inhaled route
    • Candidate drug for treatment of COPD identified within 9 months of project initiation
  • Optimizing treatments for lung cancer when delivered directly to the lungs

Using our PhenoFocus phenotypic screening assays, we are able to investigate mechanisms for their potential to impact respiratory diseases in vitro. By comparing efficacy with clinical standards of care and compounds known to have limited therapeutic efficacy in man, we can link the mechanism to the disease of interest with a high degree of confidence.

The suitability of a potential compound for lung-focused dosing can be examined pharamacokinetically following administration to the lung either via direct (e.g., intratracheal or intranasal) or indirect (e.g., aqueous solution or dry powder) delivery. Key aspects, such as lung retention versus systemic exposures, can be quantified, and, if acceptable, progression to concept testing in the appropriate in vivo model can be initiated. Efficacy in therapeutic endpoints can be measured across a dose range and compared to any known systemic side effects measured within the same model, as well as being linked to measurement of exposure levels in the key compartments.

The in vivo models can be used to demonstrate efficacy, therapeutic index and duration of action, facilitating dose-to-man predictions. This is a critical feature which reveals not only the suitability of the compound for dosing devices used clinically, but also the potential to combine with existing therapies. Early signs of irritancy can also be assessed in these efficacy studies.

Contact us to discuss how we may be able to help you maximize the value of your assets and optimize patient therapies.

1 Nosenga, N. Can you teach old drugs new tricks? Nature. 534, 314-316. (16 June 2016).