When a promising therapy moves from the lab bench to the clinic, the stakes are as high as they can get. Early-phase clinical trials, those first-in-human studies, are where years of research and millions in investment meet the unpredictable reality of human biology. For biotech innovators, this stage is a thrilling goal achieved through years of work, but it is also perilous. It’s the moment that determines whether a molecule becomes a medicine or fades into obscurity. Yet, despite its importance, early-phase success remains elusive: whilst 70% of drugs entering phase I trials head into phase II, just 33% of experimental drugs that pass phases I and II will head into phase III. So how do companies navigate this critical juncture and turn risk into opportunity?

The High-Stakes Nature of Early-Phase Trials

Early-phase trials are designed to answer fundamental questions: Is the drug safe? How does it behave in the human body? What dose achieves the desired effect without causing harm? These studies focus on safety, tolerability, and pharmacokinetics, often with exploratory efficacy signals. But the challenge lies in balancing scientific rigor with operational efficiency. A single misstep, whether that be in protocol design, recruitment, or regulatory alignment can derail years of work, and cause further funding to evaporate.

For smaller biotechs, the pressure is even greater. Limited resources, investor expectations, and the complexity of novel modalities like mRNA or cell therapies have the potential to create a perfect storm. Traditional trial models are often unsuitable for these innovative therapies, and the margin for error is razor thin. Success demands a series of rigorous scientific method, strategic foresight and flawless execution.

Partnerships for Operational Excellence

Strategic partnerships often provide the lifeline for smaller biotechs. Contract Development Manufacturing Organisations (CDMOs) bring expertise in regulatory compliance, site management, and data sciences, along with global networks for recruitment. For many small biotechs, CDMO collaboration is essential. The key is choosing partners with early-phase specialisation and proven experience in your therapeutic area. These alliances can accelerate timelines, reduce risk, and free internal teams to focus on innovation.

One of the key advantages of CDMOs is that they work closely with sponsors to develop robust, scalable formulations. The key advantage here is that through their CDMO partnerships, biotechs are able to demonstrate a clear path to formulation scale up and commercialisation. CDMOs can optimise manufacturing processes for efficiency, quality, and regulatory, thereby reducing the number of handovers and which reassures investors in the early stages of drug development.

Regulatory Alignment and Forward Planning

Regulatory engagement is another cornerstone of success. Frequent, transparent communication with regulators not only reduces uncertainty but also builds confidence among investors. This is a critical factor for smaller biotechs under pressure to deliver milestones.

While Phase I feels like the finish line, it’s really the launchpad. Planning for Phase II should begin early, with clear go/no-go criteria based on PK/PD data, biomarker strategies, and adaptive design options. This foresight keeps development momentum and reassures investors that the programme is built for continuity. For biotechs, working with a CDMO can be particularly beneficial at this point, as it provides investors with the security that their project can continue with the same company. CDMOs can also support with developing strategies for pathways to commercialisation that provide investors with a concrete plan for success.

Turning Challenges into Breakthroughs

Early-phase trials are high-stakes, high-reward endeavours. They demand a delicate balance of scientific rigor, operational agility, and strategic vision. Those who navigate this stage wisely will be designing flexible protocols, selecting sites for speed, leveraging real-time data, prioritising participant experience, and engaging regulators early. The reward is a successful trial and the foundation for future breakthroughs.

For biotech innovators, early-phase success is about eliminating risk as much as possible and managing remaining risk intelligently. For biotechs, it’s about acknowledging the common failure associated with early phase clinical trials, converting that uncertainty into opportunity and laying the groundwork for therapies that change lives.