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Building for Success: Aligning Preclinical and Phase 1 Strategy with Commercial Goals 

- PMLiVE

- PMLiVE

This article concludes our three-part series on preparing cell and gene therapies (CGTs) for successful launch and long-term viability. The first article explored the unique scientific and logistical challenges of CGT and the global outlook for access and scalability. The second focused on European expansion, highlighting the need for agile infrastructure, local expertise, and strategic partnerships to navigate fragmented payer systems and evolving regulatory frameworks. 

In this final instalment, we shift focus to the earliest stages, preclinical and Phase 1, examining how embedding commercial thinking from the outset—across regulatory, clinical, manufacturing, and access planning—can position CGT assets for broad, timely, and economically sustainable patient access. 

Strategic planning in a global regulatory landscape 

Regulatory timelines vary widely, so planning for cell and gene therapy needs to start early and should be done from an international perspective. The U.S. FDA has accelerated pathways, allowing faster access to promising treatments, but the European Medicines Agency (EMA) centralized process can be sloweri. Saudi Arabiaii, UAEiii, Canadaiv, and Israelv routinely accept leading authority approval such as the U.S. FDA, which speeds up the process significantly. In contrast, many European authorities have a bespoke system that adds time. Consequently, the traditional U.S.-then-EU launch sequence is now often not the standard process. During planning, companies may prioritize these markets in their launch sequences over those that require a full review, and this will then be incorporated into trial and commercialization plans from the start. 

At the same time, regulatory innovation, particularly in the U.S., is reshaping how developers think about platform design and portfolio strategy. Regulatory pathways in cell and gene therapy remain different across regions. The FDA has also begun to champion platform technologiesvi – standardized genes can stay largely unchanged while the very small percentage that is needed is swapped. By agreeing to review only the new, active portion of a construct, while treating the rest as previously qualified, this enables a one asset biotech to widen its portfolio with relative speed and economy.  

The signal to developers is clear: invest early in a robust, modular platform. The regulatory path for follow on assets could then prove markedly faster and less resource intensive.  

Designing Trials for Market Success 

As strategic planning continues into clinical development, aligning study design with regulatory and payer expectations becomes increasingly critical. Regulators and payers are placing greater scrutiny on the suitability of early-phase clinical endpoints. The FDA has been accepting surrogate biomarkers for accelerated approvalvii – granting early approval based on biomarkers looking at protein or gene expression rather than direct clinical outcomes. In contrast, European regulators typically require demonstrable clinical benefit. Where possible, all clinical study designs should therefore balance biomarker data with clinically meaningful measures to satisfy both regulatory and reimbursement requirements. 

Demonstrating durability of response is also becoming a key expectation, particularly in cell and gene therapies. While rapid clinical trials may accelerate timelines, they may not allow sufficient time to show how long a therapy’s effects last, an increasingly important consideration for both regulators and payers assessing long-term value. As such, trial designs must strike a balance between speed and the ability to generate robust, durable data. 

To navigate these differing expectations, early engagement with key stakeholders is essential. Involving regulators, payers, clinicians and patient representatives early in the design of a pivotal study helps determine which primary and secondary endpoints will satisfy both market-authorisation and reimbursement decisions. This engagement can also clarify acceptable study populations, for example, while the FDA may accept single-arm designs, the European Medicines Agency (EMA) often expects placebo-controlled or historical-control trials. 

Building for commercial viability 

Market-sizing exercises must go beyond prevalence estimates to reflect the real-world complexity of delivering cell and gene therapies. Diagnostic attrition, referral patterns, and treatment site capacity, all influence the true addressable market. Scenario modelling supports realistic revenue projections and builds investor confidence. In parallel, early pricing research should benchmark expected value-based-pricing ceilings against projected COGS to ensure economic viability. 

Patient identification, diagnostic pathways and treatment logistics vary significantly by geography. In Western Europe, there is a more dense network of qualified centers so patients often travel  shorter distances for treatmentviii, while in other regions, travel distances can be longer due to larger geographies. In several countries, underdiagnosis remains a primary barrier to treatment. To refine uptake forecasts, companies should quantify undiagnosed prevalence and, where appropriate, support newborn or diagnostic screening programs. 

Infrastructure readiness is a critical enabler of access. Documenting existing centres experienced in advanced therapies helps reduce training burdens and accelerates rollout. However, readiness goes beyond clinical capability, companies must assess whether sites have the necessary cryogenic storage, trained personnel, and logistical support to deliver therapy safely and efficiently. Cold chain constraints, particularly for −196 °C cryogenic shipments, must be mapped early. Aligning with specialist logistics providers and distributors in advance helps protect timelines and product integrity, especially in regions with limited infrastructure or long transit routes. 

Manufacturing strategy also plays a pivotal role in commercial viability. Cost of Goods Sold (COGS) can cap the achievable price of a therapy and directly impact profitability. As a result, investors increasingly favour asset-light approaches, such as outsourced or modular manufacturing, over capital-intensive in-house facilities. To support future scalability and cost-efficiency, organisations should: 

  • Validate a manufacturing process that reflects projected commercial scale, reducing the need for costly comparability studies later. 
  • Partner with Contract Development and Manufacturing Organisations (CDMOs) that offer flexible capacity and can scale with the program. 
  • Integrate real-time analytics to support regulatory compliance and long-term cost control.  

No single organisation controls all competencies required for successful cell and gene therapy development. Success depends on early collaboration with a network of partners: CDMOs for manufacturing, regulatory associates and local affiliates for agency engagement, logistics providers for ultra-cold-chain distribution, diagnostic networks for patient identification, and commercialisation partners such as Uniphar, that offer integrated market access, distribution reach, and data-driven insights across multiple regions. 

By understanding and addressing these access requirements early, companies can reduce risk, accelerate time-to-market, and ensure that promising therapies reach patients who need them.  

 

Conclusion 

In cell and gene therapy, early-phase planning that integrates global regulatory complexity, pragmatic clinical design, scalable manufacturing, and realistic commercial expectations provides a clear strategic advantage. Embedding these considerations from the pre-clinical and Phase 1 stages positions assets not only for regulatory approval but also for broad, timely, and economically sustainable patient access.  

Partnering with an organisation like Uniphar can help align these critical workstreams – bringing together global CGT expertise, regional regulatory and distribution support, real-world evidence generation, and deep market insight, all under one roof. 

This content was provided by Uniphar

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