The biotech playbook is in desperate need of an update

There's a well-trodden path in drug development, a kind of "traditional playbook" largely written by Big Pharma. For a small biotech, it can feel reassuring to follow these established steps. It seems like the safest route. But here’s the uncomfortable truth: for many lean, fast-moving biotechs, this traditional playbook isn’t just a poor fit; it can be a direct route to inefficiency, wasted resources, and ultimately, failure.

It's like a nimble speedboat trying to navigate by a cruise liner's charts and operating manual. The scale, the resources, the acceptable timelines, the very definition of risk, they're all profoundly different. This isn't about criticising Big Pharma; it's about recognising that what works for a billion-dollar behemoth with a vast portfolio is often misaligned with the realities of a biotech betting its future on one or two key assets.

Why the traditional biotech playbook isn't the answer

The Cracks in the "Traditional Playbook" for Small Biotechs

So, where does this well-intentioned but often flawed approach go wrong for smaller players?

• The Fallacy of Linear Development (Waterfall Woes): The old playbook often depicts drug development as a stately, linear march: Phase I, then Phase II, then the grand, expensive Phase III, followed by regulatory submission. This "waterfall" approach, where one stage must largely conclude before the next begins in earnest, is riddled with inefficiencies for biotechs. The biggest issue? Late-stage failure is utterly catastrophic when you’ve poured most of your limited cash and several years down a rigid, pre-defined path. There are too few feedback loops, too few opportunities to learn, adapt, or, crucially, kill unpromising programmes early and cheaply before they consume your entire runway. You only discover the fatal flaw when you’re closest to the finish line – and furthest from your last funding round.
  
  
• Borrowing Big Pharma’s Bulk (When You’re Built for Speed): Big Pharma companies typically operate with vast resources, diverse pipelines (meaning multiple shots on goal), and the ability to absorb the costs of large, sometimes sprawling, clinical trial programmes and longer development timelines. Their internal processes, data requirements, and strategic decision-making reflect this scale and risk tolerance. Small biotechs, on the other hand, usually have a very focused pipeline – often a single lead asset – and a runway measured in months, not years. Adopting scaled-down versions of Big Pharma’s comprehensive (and expensive) data generation strategies, such as embarking on massive Phase III programmes without crystal-clear differentiation or getting bogged down in complex internal procedures designed for much larger organisations, can be a death knell. You end up building an evidence package for a different kind of company with different kinds of problems.
  
  
• The Agility Deficit (Trying to Steer a Battleship with Oars): The traditional playbook, by its very nature, can be cumbersome, slow to react, and resistant to necessary change. It often enshrines a plan made years in advance. But science moves at lightning speed. New discoveries emerge, the competitive landscape shifts, understanding of disease evolves, and regulatory expectations can subtly change. Small biotechs must possess the agility to pivot smartly based on new data (their own, a competitor's, or emerging real-world evidence), changing market needs, or fresh insights. The old playbook often lacks the inherent flexibility and rapid decision-making mechanisms required to navigate this dynamic environment effectively. You risk sticking rigidly to an outdated plan while the world changes around you.

A Smarter Way: Principles for a Modern Biotech Playbook

If the old way is broken for biotechs, what’s the alternative? It’s about being lean, agile, and ruthlessly strategic with your evidence generation.

• Embrace Iterative Learning & Early Validation (The Agile Mindset): Instead of that long, linear march, think in shorter sprints with clear learning objectives. Focus on generating decision-informing data as early and efficiently as possible. Ask constantly: "What is the minimum viable evidence we need to answer our next key question, de-risk this programme for the next stage, or validate this assumption?" This might mean smaller, smarter, more focused studies in early development. Crucially, incorporate real-world evidence (RWE) from the outset. Use RWE to truly understand the disease context, patient heterogeneity, current treatment pathways, and potential real-world hurdles before you commit to designing large, expensive trials. This proactive learning minimises surprises later on.
  
  
• Strategic Evidence Planning as Your Compass (The Lean IEP Advantage): This is non-negotiable for a resource-constrained biotech. A lean, dynamic Integrated Evidence Plan (IEP) isn’t a bureaucratic checkbox; it's your strategic roadmap. We’ve talked about this before, but it’s central to breaking free from the old playbook. An effective IEP ensures every piece of evidence you generate whether from a clinical trial, an RWE study, health economics research, or patient-reported outcomes – is directly and explicitly tied to a critical strategic objective. This could be securing investor confidence for the next round, satisfying a specific regulatory concern, or clearly articulating the value proposition for future payers. This disciplined approach prevents the "evidence for evidence's sake" trap that the less targeted traditional playbook can sometimes encourage.
  
  
• Innovate Your Development Model (Not Just Your Molecule): Your innovation shouldn't stop at your science. Challenge baked-in assumptions about how drugs are developed. Are there more efficient trial designs for your specific situation? Could adaptive trial designs, basket trials, or master protocols provide answers faster, with fewer patients, or allow you to test multiple hypotheses simultaneously? Can you intelligently leverage RWE to create robust external control arms (where appropriate and with careful consideration of regulatory acceptance), enrich your trial data with real-world context, or model outcomes to reduce the sample size or duration of prospective studies? Think about demonstrating real-world value from day one, not just clinical efficacy as defined in a trial setting. How will your drug actually be used, and what outcomes truly matter to patients and physicians in routine practice? RWE is your key to unlocking these insights.

RWE: The Linchpin in the Modern Biotech Strategy

Real-world evidence is arguably one of the most powerful enablers for this modern biotech playbook. It’s a disruptive force that allows smaller companies to operate with a level of insight and efficiency previously difficult to achieve without massive infrastructure. RWE helps you:

• Deeply understand unmet medical needs and patient journeys.
• Optimise clinical trial design and improve site selection and patient recruitment.
• Contextualise your clinical trial results against real-world outcomes.
• Support regulatory dialogue with supplementary evidence.
• Build a compelling value narrative for payers well before launch.

Effectively, RWE allows you to make smarter decisions faster, often at a lower cost than relying solely on traditional, prospectively collected clinical trial data for every question. It helps you punch significantly above your weight.

“Innovation doesn’t start and stop with the asset”

The traditional biotech playbook, born from a different era and a different scale of operation, isn't inherently "wrong." It's just frequently the wrong tool for today’s nimble, resource-focused biotech striving to make a big impact with limited means. Your greatest strength as a biotech lies in your capacity for innovation  and that innovative spirit must extend to how you develop your therapies, not just what you develop.

Embracing agility, committing to rigorous and strategic evidence planning, and leveraging the transformative power of real-world evidence aren't just alternative approaches anymore. For small biotechs aiming to succeed in a fiercely competitive and complex environment, they are rapidly becoming the essential components of a new, more effective playbook. It's about defining your own path, guided by smart data and strategic foresight