Drug Discovery Today Volume 00, Number 00 December 2014
EDITORIAL
editorial Youssef L. Bennani
Drug hunters incorporated! Is there a formula? Drug discovery remains a highly unpredictable area of investment within the pharmaceutical sector, particularly when innovation-based differentiation is the strategy. Massive annual investments flow into this sector, despite the low success rate of about 10% [1], even when accounting for ‘me-too drugs’! The challenges in achieving a predictable and reliable portfolio-output are numerous (clinical candidates molecules suffer from lack of clinical translational biology, idiosyncratic toxicology findings, poor program execution, competition, positioning, among others) and remain ill controlled. Regardless, it has now become clear, as measured by these attrition rates at large or medium-size pharmaceutical companies, that managing large project portfolios and implementing kill-decision points at every corner, has not produced the intended results. The recent emergence of small biotechnology or biopharmaceutical companies as a new business model, which tends to mostly be forced to focus on one lead clinical asset, has changed the landscape of portfolio management and prediction thereof. However, for these smaller companies, the large majority fall victim of ‘live-or-die’ by your most advanced asset, resulting in no change in success rates for the industry.
So, pharmaceutical management at large or small scales, has still not solved the puzzle of how to increase this rate of return, despite scientific advancements, massive funding (http://m.wsj. Q2 com/articles/where-in-the-human-body-venture-capital-is-going1410724817?mobile=y), and various re-organizational and decision-making paradigms! There has been no lack of such activities to try to address the problem: numerous mergers and acquisitions, internal restructuring, job shedding, portfolio focusing and jointventure (academic and cross-companies) deals, as drivers for innovation, sustainability and value creation. The jury is still out as to which of these partnership models will help turn the tide. So what to do? Regardless of company size, focused approaches, ‘innovative’ strategies or execution abilities, every pharmaceutical company still needs ‘drug hunters’. Over the last twenty years or so, I often heard the two words together: ‘Drug hunter’, with regards to particular individuals, but have struggled in defining what qualifies such individual(s). Naturally, if we can crack this formula, perhaps we can ‘clone’ the model and drive to success. This begs the following questions, in a similar way to Leaders: how to identify them? Can we develop them? Is the model scalable? Or are they born this way? So what makes a scientist a drug hunter [2]? I would start with the obvious pre-requisites: A solid scientific pedigree, with a number of bench-years’ experience (this is an important step: getting one’s hands wet, on the ground is priceless). An in-depth, quasi-encyclopedic knowledge of all drugs successes, drug failures and how they came about, including structures and targets, approaches. A voracious appetite for data (all sorts of project related data), to feed their ‘connectome’ (a pre-wired synaptic firing map). An acute attention to structure–failure relationships (SFR): what structural (chemical and/or topological) features cause chemical or biological issues that negatively affect aspects such as solubility, ADME-Toxicology, or tissue accessibility, among others. A mastery of general features to avoid in failed drugs, or to build into successful molecules, which is actually called ‘medicinal chemistry’.
www.drugdiscoverytoday.com Please cite this article in press as: Bennani, Y.L. Drug hunters incorporated! Is there a formula?, Drug Discov Today (2014), http://dx.doi.org/10.1016/j.drudis.2014.11.012
1359-6446/06/$ - see front matter ß 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.drudis.2014.11.012
1
DRUDIS 1543 1–2 EDITORIAL
Editorial
Now on to perhaps the less obvious pre-requisites, as one could even ask if it is an art, science, or a balance of the two? Or is it more fishing than hunting? The following ‘list’ is also quite prevalent in ‘drug hunters’: A fine personality-balance between tenacity (know when to let go) and flexibility (accommodate other perspectives). An ability to ‘see the invisible’ through data-connecting and emerge with new perspectives. A subtle ability to lead teams or projects, with bold perspectives, into non-obvious terrain. Asking the right questions, without being biased by dogma or rules, about human disease and how to translate that into a hypothesis-experiment-result (the scientific method!). Leading by inspiring colleagues to think differently (nothing ever came out of repeating the same experiment). I liken to compare ‘drug hunters’ to ‘good artists’, whose artwork might not at first be appreciated, but, once established it garners top dollar. I also wonder if it is necessary to have the hunter spirit (more aggressive, opportunistic and one-way ‘kill-driven’); or more of a fisherman perspective (patient, right bait, right time
2
Drug Discovery Today Volume 00, Number 00 December 2014
and an ability to let go, if it is not the right catch). In my experience, drug hunters come in different flavours (education, years of experience and personalities) and may not necessarily associated with an approved drug, given more often than not, the approval process is completely outside of their control. The latter is a function of competition, clinical output, and business decisions. It actually is quite a miracle that should be world-celebrated, when a drug actually gets approved and is safely adopted by patients. So, invitation is open to devise a formula or rule for the above; as the saying goes: ‘je ne cherche pas, je trouve’? By Pablo Picasso. References 1 Hay, M. et al. (2014) Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40–51 2 Black, J. (2005) A personal perspective on Dr Paul Janssen. J. Med. Chem. 48, 1687–1688
Youssef L. Bennani Vertex Pharmaceuticals (Canada) Inc., 275 Armand Frappier, Laval, QC H7V 4A7, Canada email: [email protected]
www.drugdiscoverytoday.com Please cite this article in press as: Bennani, Y.L. Drug hunters incorporated! Is there a formula?, Drug Discov Today (2014), http://dx.doi.org/10.1016/j.drudis.2014.11.012
EDITORIAL
editorial Youssef L. Bennani
Drug hunters incorporated! Is there a formula? Drug discovery remains a highly unpredictable area of investment within the pharmaceutical sector, particularly when innovation-based differentiation is the strategy. Massive annual investments flow into this sector, despite the low success rate of about 10% [1], even when accounting for ‘me-too drugs’! The challenges in achieving a predictable and reliable portfolio-output are numerous (clinical candidates molecules suffer from lack of clinical translational biology, idiosyncratic toxicology findings, poor program execution, competition, positioning, among others) and remain ill controlled. Regardless, it has now become clear, as measured by these attrition rates at large or medium-size pharmaceutical companies, that managing large project portfolios and implementing kill-decision points at every corner, has not produced the intended results. The recent emergence of small biotechnology or biopharmaceutical companies as a new business model, which tends to mostly be forced to focus on one lead clinical asset, has changed the landscape of portfolio management and prediction thereof. However, for these smaller companies, the large majority fall victim of ‘live-or-die’ by your most advanced asset, resulting in no change in success rates for the industry.
So, pharmaceutical management at large or small scales, has still not solved the puzzle of how to increase this rate of return, despite scientific advancements, massive funding (http://m.wsj. Q2 com/articles/where-in-the-human-body-venture-capital-is-going1410724817?mobile=y), and various re-organizational and decision-making paradigms! There has been no lack of such activities to try to address the problem: numerous mergers and acquisitions, internal restructuring, job shedding, portfolio focusing and jointventure (academic and cross-companies) deals, as drivers for innovation, sustainability and value creation. The jury is still out as to which of these partnership models will help turn the tide. So what to do? Regardless of company size, focused approaches, ‘innovative’ strategies or execution abilities, every pharmaceutical company still needs ‘drug hunters’. Over the last twenty years or so, I often heard the two words together: ‘Drug hunter’, with regards to particular individuals, but have struggled in defining what qualifies such individual(s). Naturally, if we can crack this formula, perhaps we can ‘clone’ the model and drive to success. This begs the following questions, in a similar way to Leaders: how to identify them? Can we develop them? Is the model scalable? Or are they born this way? So what makes a scientist a drug hunter [2]? I would start with the obvious pre-requisites: A solid scientific pedigree, with a number of bench-years’ experience (this is an important step: getting one’s hands wet, on the ground is priceless). An in-depth, quasi-encyclopedic knowledge of all drugs successes, drug failures and how they came about, including structures and targets, approaches. A voracious appetite for data (all sorts of project related data), to feed their ‘connectome’ (a pre-wired synaptic firing map). An acute attention to structure–failure relationships (SFR): what structural (chemical and/or topological) features cause chemical or biological issues that negatively affect aspects such as solubility, ADME-Toxicology, or tissue accessibility, among others. A mastery of general features to avoid in failed drugs, or to build into successful molecules, which is actually called ‘medicinal chemistry’.
www.drugdiscoverytoday.com Please cite this article in press as: Bennani, Y.L. Drug hunters incorporated! Is there a formula?, Drug Discov Today (2014), http://dx.doi.org/10.1016/j.drudis.2014.11.012
1359-6446/06/$ - see front matter ß 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.drudis.2014.11.012
1
DRUDIS 1543 1–2 EDITORIAL
Editorial
Now on to perhaps the less obvious pre-requisites, as one could even ask if it is an art, science, or a balance of the two? Or is it more fishing than hunting? The following ‘list’ is also quite prevalent in ‘drug hunters’: A fine personality-balance between tenacity (know when to let go) and flexibility (accommodate other perspectives). An ability to ‘see the invisible’ through data-connecting and emerge with new perspectives. A subtle ability to lead teams or projects, with bold perspectives, into non-obvious terrain. Asking the right questions, without being biased by dogma or rules, about human disease and how to translate that into a hypothesis-experiment-result (the scientific method!). Leading by inspiring colleagues to think differently (nothing ever came out of repeating the same experiment). I liken to compare ‘drug hunters’ to ‘good artists’, whose artwork might not at first be appreciated, but, once established it garners top dollar. I also wonder if it is necessary to have the hunter spirit (more aggressive, opportunistic and one-way ‘kill-driven’); or more of a fisherman perspective (patient, right bait, right time
2
Drug Discovery Today Volume 00, Number 00 December 2014
and an ability to let go, if it is not the right catch). In my experience, drug hunters come in different flavours (education, years of experience and personalities) and may not necessarily associated with an approved drug, given more often than not, the approval process is completely outside of their control. The latter is a function of competition, clinical output, and business decisions. It actually is quite a miracle that should be world-celebrated, when a drug actually gets approved and is safely adopted by patients. So, invitation is open to devise a formula or rule for the above; as the saying goes: ‘je ne cherche pas, je trouve’? By Pablo Picasso. References 1 Hay, M. et al. (2014) Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40–51 2 Black, J. (2005) A personal perspective on Dr Paul Janssen. J. Med. Chem. 48, 1687–1688
Youssef L. Bennani Vertex Pharmaceuticals (Canada) Inc., 275 Armand Frappier, Laval, QC H7V 4A7, Canada email: [email protected]
www.drugdiscoverytoday.com Please cite this article in press as: Bennani, Y.L. Drug hunters incorporated! Is there a formula?, Drug Discov Today (2014), http://dx.doi.org/10.1016/j.drudis.2014.11.012
