The best worst idea

The best worst idea

Premise, promise, proof

It’s an alliterative phrase, that forms the basis for one of the worst positioning templates out there - one which essentially eliminates the positioning from the positioning.

However, it handily frames our approach to drug development - in a linear timeline: land on the idea of the drug (the premise), understand its value (its promise) and then deliver all the proof that promise needs.

The challenge of the traditional approach is that the premise is often derived from the proof, which is the wrong way around - it tends to lead to the collection of obvious evidence, the lowest hanging fruit, rather than more interesting (or more valuable) evidence. Remember that your drug is approved not based on what it is, but what it has shown. What it has shown is a product of what you chose to collect.

Our approach begins at phase I, when the spectrum of available premises should be explored - the creation of multiple TPPs - against which futures can be understood: what is the risk of developing this idea, in terms of regulatory risk, technical and financial risk, what is the financial opportunity from this idea (specifically), and how might we get there. Doing this working out before the plans for phase II start allows for real proof of ‘concept’ (or premise) to be collected - or at least, enough to provide confidence in further development towards this target.

‘Proof’ has levels, but proof of concept is a search for clues, rather than delivery of robust proof that our drug does what we think it does. As such, our approach looks at more clues, more evidence that our drug might work in different ways. The linear approach tends to underdeliver on proof of the most basic concept, leading to phase III failing more often than it should - the predictability of phase III success from a ‘successful’ phase II has barely changed in decades, even on the most direct paths. Developing a broader understanding of our drug against a range of opportunity profiles may lead to more confidence in phase III, but it will certainly give more confidence in a phase III that otherwise might never have been explored - one which may well be the ideal launch profile.

As a guide for development, exploring a range of premises, understanding the spectrum of promise and then delivering proof of the best makes the most sense. In that order. The worst way of doing positioning is also the best way to develop drugs.

Zhen Su, MD MBA

Physician-scientist, CEO and Entrepreneur at Marengo Therapeutics A dreamer, strategist and doer with passion to improve cancer care.

1 个月

Excellent work Mike! Very relevant to any development team no matter a large organization or a small startup.

Nancy Paynter

Life Science Leader and Strategist. Passionate about fostering innovation and traction at the intersection of commercialization, patient-centeredness and tech-enablement

1 个月

So helpful as we work to rethink established portfolio planning frameworks. Thank you! Interesting too, to consider the word choice of "proof" as it inherently is biased in favor of pharma's self-defined "promise" that is anchored to an effort to optimize whatever "premises" a company has to work with in its existing war chest (as shared with Wall Street). It might be interesting to overhaul the three Ps to build a more relevant (sustainable?) discovery machine that starts from the outside and works inward-- to uncover real world need (vs "proof"), implications for strategic discovery targets (new approach to establishing a "premise") and then -- optimize data models to understand "real world promise" (longer-tail business upside/portfolio opportunity). The world is changing and becoming globally and technically integrated more rapidly then we realize. Why not be bold and look beyond corporate walls to truly solve for external needs in new ways?

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