Ah, but I was so much older then. I'm younger than that now
One of the glories of phase I is that it is so innocent, so open to possibility.
I remember learning the idea of neoteny during my Genetics degree - the idea that holding onto youth for as long as we do is one of the things that differentiates humans and their ability to learn for longer. Being nurtured for many more years than our animal competition means more time to develop cognitively before we have to go and do something useful - but in that time, in that safe space, we develop extraordinary abilities.
In the time since I was at university, neoteny has changed emphasis - rather than holding onto youth as a development stage for longer, it now is more used to suggest the retention of juvenile features in the adult stage. I prefer that older definition - partly because it is more akin to the IDEA philosophy of early stage - that it can be used to explore and learn, rather than something to be gotten through as fast as possible.
Pharma tends to the ‘get it over with as quickly as possible’ - it is a safety hurdle, and once beyond that phase the ‘real work’ can get underway. No-one gets excited about pI results. Lots of people get excited about good phase IIs. In a linear development pathway, that makes sense. However, we need to challenge the idea that a linear development pathway makes sense, in itself.
Development is directed, towards a launch destination. That launch destination can be carefully derived, or be a good/ quick best guess, corrected on the go. The latter is more likely to be in place in pharma development - guessing launch conditions for a timeline that can run 8-10 years hence can seem nonsensical, in terms of accuracy of information. Of course that is true. But it is equally true for the quick best guess as for the dozens of other launch destinations that weren’t calculated.
Whatever phase I is for, the critical decision point is ‘what do we study at phase II?’ This pre-phase II point, then, should be assessing a variety of launch profiles against each other - for attractiveness, and probabilities of success. More often, however, an obvious or default path is green lighted based on positive safety signals. And, from then, nothing other than a go/ no go for the obvious or default path can be determined from pII or pIII. The label that the drug might launch with is drafted going into that critical decision point - pre-phase II.
It is rare, when we’re doing the work, that a molecule doesn’t produce 10-20 different launch profiles, which of course vary enormously in the areas of cost to develop, risk of development, time in development and value on market. The range itself is the goal - comparing and contrasting very different options, outside of the traditional boundaries of indication, or even therapeutic area. Presenting to a head of R&D with a range of permutations, instead of a single linear path, means that portfolios can be developed with more depth and range, instead of more or less technical risk.
Holding onto the opportunity of early phase for longer is akin to neoteny - allowing a more directed, opportunistic development that might have been missed in a traditional process. Molecules need time, and space, to show what they’re good at, and for companies to evaluate different kinds of unmet need, or market opportunity. The closer those two things come, the better for everyone.
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