The ability to make disciplined, well-informed decisions around pharma strategy and portfolio prioritization in biopharma is more important than ever today. With capital markets in flux, regulatory headwinds, and ever-present scientific risk, boards and executives must balance patient impact, financial discipline, and long-term vision. In this Q&A, Shalini Sharp, an experienced board member (currently at BeiGene, Septerna, Neurcrine Biosciences, Organon, and Mahzi Therapeutics) and former biotech CFO (at Ultragenyx Pharmaceuticals, Inc. and Agenus), shared her insights with me on best practices, pitfalls, and the evolving landscape of pharma strategy.
Q: With so much pressure on teams and boards to make high-fidelity decisions, how do you approach portfolio and budget prioritization?
A: It starts with a big-picture strategic vision — where do we want to be in five, ten, or twenty years? We work backward from that vision to this year’s operating plan, identifying key programs and their costs. If we can’t fund everything, we prioritize based on each asset’s probability of success, potential patient impact, and the cost-benefit trade-offs. We often run scenario analyses, like the Net Present Value (NPV) impact of delaying or accelerating programs, to guide our choices.
Q: What factors should teams consider when assembling a portfolio plan?
A: Teams need to assess multiple different factors. The key considerations for me include:
- Patient population size and unmet need
- Competitive landscape and differentiation
- Mechanism of Action (MoA) and Probability of Success (PoS)
- Manufacturability and scalability
- Time and cost to clinic/market
- Commercial infrastructure and go-to-market capabilities
- Market opportunity, exclusivity, and IP protection
- Financial modeling of outcomes, pricing, and reimbursement
It’s very important to compare all assets objectively to make informed portfolio decisions.
Q: What should leadership do when programs don’t pan out?
A: Anticipate points of failure and proactively mitigate risks, but recognize that surprises are inevitable. When a setback occurs, ask why it happened, if it’s fixable, and whether it’s worth fixing. Emotional attachment to programs, especially in programs targeting rare diseases, is common, but rational, disciplined decision-making is vital to your overall success. Sometimes fixing an issue can lead to new opportunities like a manufacturing glitch, can lead to a new patent or better outcomes, but it’s important for decision makers to be clear-eyed about when to continue with a program and when to move on.
Q: How does one effectively balance science, finance, and commercial potential?
A: The best decisions come from executive teams with a cross-functional view, not from those that operate in scientific, commercial, or financial silos. Bias is inevitable, so set clear go/no-go criteria up front and ensure decisions are data-driven and mission-aligned. The CEO and other C-suite leaders must be able to see the whole picture and make objective decisions. Bias is inevitable, especially when people are emotionally invested. That’s why it’s critical to set clear go/no-go criteria up front and stick to them, unless there is new information, to ensure that your decisions are data-driven and mission-aligned.
Q: How can company culture support better pipeline decisions?
A: A mission-driven culture, with patient impact as the North Star, is essential, and objectivity is equally important. Be willing to walk away if the data doesn’t support a program. Transparency and communication are key. For example, in one organization, we took calculated risks with compassionate use programs, which not only helped patients but also generated valuable data for regulatory filings. Sometimes, counterintuitive decisions, like setting pricing lower to speed up access, can boost both patient and business outcomes
Q: In your view, what’s the biggest threat to a company’s portfolio strategy today?
A: Policy changes are a major driver in portfolio strategy. Recent cuts in the National Institutes of Health (NIH) and the Food & Drug Administration (FDA) funding threaten innovation and regulatory capacity. Another example of policy influencing strategy is the Inflation Reduction Act, where shifting drug pricing dynamics sometimes creates perverse incentives, like deprioritizing small molecules or changing clinical development sequencing of indications. Incentives for rare diseases are also uncertain. This environment increases risk aversion, making global diversification more attractive.
Q. How do you weigh in-licensing versus internal development?
A: It’s important to analyze both in-licencing and internal opportunities in the same way. The science and business fundamentals matter more than the origin of the asset. Portfolio committees should use the same frameworks for internal and external assets. The only exception is for true platform companies, where the pipeline is inherently homegrown. “Not built here” is never a good reason to deprioritize a promising opportunity.
Q: What advice do you have for companies prioritizing rare disease assets?
A: The fundamentals remain the same: rare diseases often have more straightforward biology, less competition, and lower infrastructure requirements. Incentives like orphan drug exclusivity and tax credits still help, but with risk-averse capital markets, companies may need to reposition assets for broader indications, seek strategic partners, or pursue non-dilutive funding from advocacy groups, foundations, or government sources. Practical, proactive funding strategies are increasingly necessary. Rare disease will come back into favor when new success stories emerge, but for now, sometimes some practical and creative decisions may be necessary to keep programs moving.
Q: What is the future of pharma strategy and portfolio prioritization?
A: Success will require a rigorous, objective, and patient-centric approach. Leaders must break down silos, adapt to policy and market shifts, and make tough calls with integrity. Whether expanding globally, balancing internal and external innovation, or focusing on rare diseases, a clear vision, transparency, and unwavering focus on patient impact will drive meaningful progress.
Thank you, Shalini, for sharing these insights with me and the Vibe Bio community! We know that biopharmas struggle to navigate pharma strategy and portfolio prioritization in today’s complex landscape; however, now is the time to embrace disciplined, data-driven decision-making. It’s possible to balance innovation, risk, and commercial focus by leveraging new technologies, such as AI-powered pipeline analysis, to adapt quickly and maximize both patient and business impact in a rapidly changing business and regulatory environment.
Learn how VibeOne’s AI-powered portfolio analysis helps you make better decisions, faster.
Photo by Hendrik Morkel on Unsplash
