Non-clinical Discovery

Leading to proof of concept in vitro/in vivo (if required) that will feed into the justification to progress to a clinical trial.

The overall aim of this phase is to generate the necessary evidence, in appropriate model systems, that your repurposing candidate medicine has the potential to deliver a beneficial effect in patients. This will include demonstration of likely efficacy and safety and may involve proving that your repurposing candidate interacts with the target biological pathway in the right way. At the end of this phase you should have collected enough evidence that the treatment will be safe and effective to progress to the next development stage. The amount of evidence required will vary considerably between projects and will depend on what existing evidence can be drawn on to support progression and how different the new use is from the existing use.

Main activities and considerations:

Amount and type of data

  • How much, and what type of, novel non-clinical data generation is required for your next steps?
  • How much relevant data is already available that you do not need to replicate or duplicate?
    • Sources could be the originator company, relevant clinical networks, publications, patient groups, charities and searching for existing or previous trials
  • Early engagement with the regulator is important to understand what non-clinical data might be needed to support future clinical trial authorisation applications 
  • Consider MHRA scientific advice to clarify the requirements. There is often a fee (~£3000--£5000) for this service, though it is always free for rare, paediatric conditions. Funders may be able to support this fee.

Data generation

  • Where, and by whom, will the data be generated?
  • If you are an academic group it is likely that this phase of development will be conducted in your lab, or by a collaborator.
  • If you are a patient group you may wish to partner with a relevant academic group or fund relevant studies at a contract research organisation.
  • How will the data be captured and reported, if not done 'in-house'? If outsourced, make sure that the outputs are in an appropriate format and in sufficient detail for your requirements.

Disease models

  • Are there existing disease models? If so:
    • Are they relevant and translational?
    • Are the endpoints clinically translatable?
    • Are the models available and established?
    • How will you gain access to the model(s)?
    • Would it make sense to partner with the lab or organisation that holds them? What would be the terms of such a partnership?
  • If there is no such model available does one (or more) need to be generated and characterised? Non-clinical data may not be a requirement for your programme to progress – funders and MHRA may be able to offer advice on your individual case.
  • Note: exploratory work around the mechanism of action of the drug or the mechanism of disease may not be supported as a primary objective through one of the major translational funding schemes (though such work in humans may be supported by MRC's Experimental Medicines Scheme or, at Phase 2/3, by NIHR's Efficacy and Mechanism Evaluation scheme). If you are unsure whether your work is within remit, contact the funders.

Source material for testing

  • At this early stage you will not necessarily require clinical grade material. If it is used, it must be of suitable pharmaceutical quality for the data to be relevant to support a future clinical trial.
  • If a company is supplying the material, do you have a collaboration agreement or contract in place? Visit Non-clinical Development - Contracting with the CRO

Secure funding

  • Before embarking on a repurposing project many teams will need to secure funding. If you are a patient organisation or charity you may have your own funds, or you may seek funding from other sources, for example LifeArc, MRC and/or industrial partners. Potential funders are often available to advise on the application process. Remember that this may be a lengthy process and require significant input and time.
  • Visit Funding for further information

Planning for next development phase

  • Consider scoping and costing of the Good Laboratory Practice (GLP) phase for activities required by regulators, such as safety/toxicology data generation. Visit Non-clinical Development for further information.