DOMAIN EXPERTISE


Over the past 20 years, an increasing number of drug discovery projects failed as companies prioritised therapeutic areas with theoretical blockbuster potential, without also considering the difficulty of delivering a successful therapy.


ebisu work with clients to identify commercial opportunities that are underpinned by strong science and have a realistic prospect of success.


Drug discovery is difficult. By the time a candidate enters clinical trials all properties governing its future performance are fixed; its likelihood to cause off-target effects and even its potential to work positively in unforeseen therapeutic areas.
We look at the early stages of discovery from the initiation of a project until preclinical, in order to determine the molecular rationalle. Similarly we look carefully at how a project would be assessed in a clinical trial, as those methods may not reflect the more advanced approaches available to earlier stage discovery. In such cases a positive outcome may be inherently risky.


For early stage projects it is possible to use informatics techniques  to consider both the physicochemical characteristics of each target and any chemistry that has already been progressed on related targets. Such data can be scored appropriately.


However, it is much more difficult to dissect the molecular context of a target i.e. its interactions with other proteins and the downstream effects they all have. Furthermore, despite significant developments, the fact remains that much of the human genome and therefore their interactions remain poorly understood.



DOMAIN EXPERTS


It is critical to assess the knowledge of domain experts. They will have usually accumulated significant experience and can make scientific connections that are often not in the literature.


Domain experts can have a stronger track record of working with incomplete data. They can consider data in the context of considerable long-term research, the majority of which will not have been published, in particular negative results. They will also have a much stronger understanding of key research publications data from other (often competitor) groups.

 

SCIENTIFIC RIGOR


Less than twenty years ago, many compounds failed due to poor ADME and toxicology reasons. However an improved understanding of these characteristics has resulted in more compounds satisfying industry generated (but not perfect) criteria. Now many more projects pass through to Phase 1 trials.

the failure to “fail fast  & early”

Unfortunately this initial success does not follow through to a successful launch. Only later, when the costs of trials are increasing, is it found that compounds either fail to perform in the expected manner or reveal unanticipated off-target effects.



TOO MANY PROJECTS FAILING CLINICAL TRIALS?


In other words researchers have become much better as ensuring their projects pass preclinical tests which are themselves approximations of reality but little better at getting compounds through to launch.


Such observations are completely at odds with the pharma mantra for unsuccessful projects to ‘fail fast and early’.


We help companies to analyse internal project data or look at available third party information by looking at the underlying molecular data and addressing potential issues:


  1. Preclinical concentrations were unrealistically high?

  2. Actual mechanism of action is in doubt?

  3. Larger doses in animal experiments may be associated with intrinsically poor druggability of the target.

  4. The target may reside in a network that remains poorly understood?


It will be clear to the reader that there is considerable overlap with the work outlined in our zero to candidate section, the main difference being timing that the analyses are carried out

 

seed finding

DOMAIN EXPERTISE &
SCIENTIFIC RIGOR



A strong business approach needs to be matched with a rigorous technical strategy.


Our analytical capabilities allow us to assess key aspects of projects in an objective manner

READ MORE