A Smarter Shot at Success
There’s something uniquely exciting about having multiple promising early-stage assets, each with its own mechanism of action (MoA), all targeting the same therapy area or indication. For many pharma teams, this is where the old ‘multiple shots on goal’ strategy has historically been used: choose the one or two front-runners and hope at least one makes it through the gauntlet of development and regulatory approval. However, times are changing. Increasingly, companies are moving beyond hope and adopting a more intentional, portfolio-driven approach, one that aims to develop multiple assets in tandem, each with a clearly defined positioning within a broader indication or disease area strategy.
This approach isn’t for the faint-hearted. It’s complex, resource-intensive, and demands cross-functional alignment. To get it right, a fine balance of commercial, clinical, and scientific factors must be achieved, along with robust analysis and a clear communication strategy to secure the ongoing investment required via the internal governance process.
In this article, I’ll walk you through how to make it work, step by step.
Turning strategy into action: A step-by-step guide to building your portfolio
Transforming a set of early-stage assets into a cohesive, high-impact portfolio within a single disease area or indication demands a structured, calculated approach. The following steps outline how to navigate the critical decisions and trade-offs that shape successful portfolio development, from market analysis to commercialisation.
Step 1: Commercial foundations first
The first step in any portfolio strategy must be a full commercial assessment of the indication. It’s one thing to have strong science, and it’s another to have a business case that holds up. This means looking at the indication through a commercial lens. Is the market big enough? Does it have a high enough level of unmet need to support more than one new entrant? What’s the competitive timeline? Who else is coming, what will they offer, and when?
Understanding the dynamics of the market is crucial, beyond just considering its total size. This includes how the treatment landscape might evolve, where future competitors are likely to be positioned, and whether there is cross-over and meaningful room for differentiated MoAs. For multiple assets to succeed, they must offer something genuinely distinct, throughout the lifecycle of the disease and the portfolio.
Step 2: Understand and segment the patient population
Once there’s confidence that the market can support a portfolio of assets, the next step is to identify the most appropriate patients. Instead of viewing them as a single group, consider them as distinct, targetable populations within the same indication. These populations could be segmented based on biomarkers, disease subtypes, differences in clinical presentation, lines of therapy or even patient preferences around treatment delivery.
Some segmentations may be obvious, while others may require more exploration or validation with external experts. It’s essential to understand both how to segment the population and whether each segment is commercially viable. Identifying a patient subgroup that responds differently to a particular MoA is important, but it is equally crucial to determine if that subgroup is large enough, and accessible enough, to justify its own development track.
Step 3: Map out differentiation and asset roles
With both the commercial landscape and patient population clarified, attention turns to the assets themselves. The key question here is: How do these assets fit together? Can each play a distinct role in the treatment landscape? And can you articulate a scientific rationale for why each asset deserves a place in the portfolio?
This is where MoA becomes particularly important. If two assets act via fundamentally different pathways, or demonstrate differing onset times, safety profiles, or routes of administration, they may naturally align to different patient segments. Others may be better positioned as combination therapies or follow-on treatments within a treatment algorithm. Differentiation should be based on data, but it also needs to be communicated clearly, internally and externally. Without clear positioning, the value of the portfolio as a whole begins to blur.
Step 4: Shape the clinical and regulatory strategy
Clinical development for a portfolio looks and feels different from development for a single asset. Teams will need to ask whether assets can be developed in parallel, or if a staggered approach, one that leverages learnings from earlier trials incorporating exploratory end points, offers better efficiency and risk mitigation. Adaptive study designs may provide flexibility and speed, especially when applied smartly across the portfolio.
Regulatory engagement is just as important. Regulators will need to understand each asset’s individual trial design as well as the broader logic of the portfolio. If multiple products are targeting overlapping populations or building on each other’s data, that needs to be made explicit. There may be opportunities to streamline review processes, but only if the dialogue with agencies begins early. Unlike with a single asset, this requires a long-term view, early consideration of the core claims required from each asset and a willingness to think in systems rather than silos.
Step 5: Align market access and value strategy
Successfully bringing a portfolio to market requires more than just approvals, demanding a clear and coordinated value strategy across all assets. This includes detailed thinking around pricing, sequencing, and access, both individually and collectively. Each asset will need a value proposition that stands on its own but also complements the others. The overall narrative needs to make sense: Why these products, why now, and why together?
The access strategy should also account for potential risks to the portfolio, such as pricing pressures, regional access disparities, or overlap with lifecycle indications. It’s also the moment to conduct a thorough intellectual property review. Issues around patent life, extensions, or regulatory exclusivity can significantly impact portfolio sequencing and pricing flexibility down the line. These concerns have both legal and commercial implications.
Step 6: Drive efficiency through shared infrastructure
If there’s one often-overlooked advantage of a portfolio approach, it’s operational efficiency. Developing multiple assets in the same indication allows for shared clinical operations, centralised data platforms, and unified contracts with CROs or manufacturers. In many cases, supply chain and trial design infrastructure can be scaled across assets, reducing duplication and accelerating timelines.
This also allows teams to build in early decision points: milestones where data can help determine whether to advance, accelerate, pause, or stop individual development paths. Making these decisions at the right time requires trust, discipline, and a shared understanding of the bigger picture. But it’s what separates successful portfolio strategies from costly, unfocused efforts.
Final thought: It’s not about the asset; it’s about the enterprise
Perhaps the biggest success factor in all of this is mindset rather than strategy or execution. A portfolio approach only works when cross-functional teams operate with a shared goal: enterprise value. That means being ready to make tough calls. Sometimes a promising asset might need to be deprioritised in favour of another. Sometimes a team will need to accept a smaller patient population for their indication or drop down the launch sequence. And sometimes development stops altogether.
What matters is that decisions are made for the portfolio rather than individual loyalties. This takes courage, transparency, and a culture that rewards team success over individual wins. When executed well, a portfolio approach can deliver exceptional outcomes, not just for patients, but for the business, too.
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