As drug development becomes increasingly complex, early-phase clinical trials are taking on a far more strategic role than simply establishing safety. Sponsors are now expected to generate meaningful evidence that informs dose selection, supports regulatory engagement, and guides critical investment decisions much earlier in the development process. In this exclusive BioPharma Boardroom Q&A, Greg Plunkett, CEO of Accelagen, explores how adaptive trial design, cross-functional alignment, data strategy, and an approval-first mindset are helping biopharmaceutical companies navigate global regulatory pathways, accelerate development timelines, and improve the likelihood of long-term clinical and commercial success.

How is early-phase clinical trial design evolving to better accommodate increasingly complex global regulatory pathways?

Early-phase clinical trial design is evolving from a largely standardised sequencing model into a more adaptive and strategically integrated component of development. The objective is no longer simply to establish an initial safety profile, but to generate higher-value evidence that can inform dose selection, support regulatory dialogue, and shape subsequent development decisions with greater confidence. In this environment, trial design has become a key lever for both speed and strategic quality.

Historically, first-in-human studies were typically conducted in healthy male volunteers using a fixed progression from single ascending dose to multiple ascending dose cohorts, with dose escalation primarily focused on establishing tolerability. That model remains relevant in some settings, but it is increasingly insufficient for therapies with more precise mechanisms of action or higher inherent risk profiles, where evaluation in healthy volunteers may be inappropriate or ethically unjustifiable. In areas such as oncology, initiatives such as the FDA’s Project Optimus have reinforced the need for more informed and flexible dose-finding strategies. These approaches allow sponsors to reach potentially therapeutic exposure earlier, generate more decision-relevant data, and better balance patient benefit with safety oversight.

The core purpose of early clinical development remains unchanged: to establish whether a new therapy can be advanced safely. What has changed is the expectation that these studies should also generate more actionable insight, earlier in development. Modern early-phase designs are therefore not only safer and more fit-for-purpose, but also more effective in guiding capital allocation, regulatory strategy, and the overall direction of the development program.

What are the key benefits of aligning clinical, biometrics, and regulatory strategy from the outset, and where do sponsors most often face challenges?

Aligning clinical, biometrics, and regulatory strategy from the outset is fundamental to building a development program that is both execution-ready and decision-useful. When these functions are integrated early, sponsors are better positioned to design studies that generate relevant evidence, support regulatory objectives, and remain operationally deliverable. This improves the quality of decision-making, reduces avoidable rework, and strengthens the overall probability of development success.

A common challenge is the understandable desire to maximise learning from each study. However, as protocols become more complex, the risk profile increases. Extensive assessment schedules, multiple endpoints, and broad data collection requirements can create operational inefficiencies, elevate patient and site burden, and reduce consistency in execution. In practice, this can compromise data quality and limit the ability to draw clear conclusions at the points where strategic decisions are required.

This is where cross-functional alignment creates real value. Regulatory input helps define the evidence most likely to be persuasive with health authorities. Biometrics ensures the study is designed to produce robust, interpretable, and decision-ready data. The clinical operations team then translates that strategy into a protocol that can be executed effectively in the real world, while maintaining patient feasibility and study integrity. Without that alignment, sponsors are more likely to encounter delays, protocol amendments, resource inefficiencies, and data packages that do not fully support their intended objectives.

Australia is often positioned as a strategic entry point for clinical development—what advantages does it offer in accelerating global programs?

Australia offers a well-established and robust combination of regulatory efficiency, scientific quality, and capital efficiency, making it an attractive entry point for global clinical development. For early-phase sponsors, it can provide a faster path from final protocol to first patient dosed, while still generating data that are credible with most international regulators, such as the US FDA and European Medicines Agency (EMA).

A key advantage is the efficiency of the regulatory pathway. In utilising Australia’s Clinical Trial Notification (CTN) framework, studies can often achieve rapid regulatory approval, thereby avoiding regulatory delay as seen in some other jurisdictions. This can materially shorten start-up timelines to achieving patient enrolment, allowing Sponsors to generate early human data sooner. This milestone is critical for refining development strategy and maintaining program momentum.

Australia also offers access to experienced investigators, high-quality trial infrastructure, and internationally accepted standards of Good Clinical Practice. For eligible companies, the R&D Tax Incentive can further improve capital efficiency by reducing the net cost of development. Taken together, these factors make Australia more than a convenient geography—it is a strategic platform for generating early evidence, de-risking programs, and informing subsequent global expansion.

How can an “approval-first” mindset practically reduce downstream risk during early development stages?

An approval-first mindset, whereby a Sponsor thinks towards what the final product may look like on a shelf, changes the way early development decisions are made. Rather than viewing early-phase studies as isolated technical and somewhat mandatory exercises, it frames them as the first step in building a data package that will ultimately withstand regulatory, clinical, and commercial scrutiny. In having this vision front of mind, it creates greater discipline around study objectives, endpoint selection, dose strategy, and operational design from the outset.

In practical terms, this mindset helps Sponsors focus on generating evidence that will remain relevant beyond the immediate study output. It encourages earlier consideration of what regulators are likely to expect, which patient populations will be most informative, and what level of data quality and consistency will be required to support later-stage decisions. As a result, teams are less likely to pursue designs that are scientifically interesting but strategically misaligned.

The value of this approach is risk management and reduction. When development is guided by the end objective from the beginning, Sponsors can minimise unnecessary change, reduce the likelihood of inconclusive data, and improve continuity across the program. In executive terms, an approval-first mindset strengthens decision quality, preserves capital, and improves the probability that early investment will translate into regulatory and commercial progress.

Whilst maintaining an approval-first approach is extremely valuable, Sponsors also need to remain adaptable to change, such that where new data or changes in regulation may require a review of the strategy, they can seize the opportunity 

What role does data strategy and biostatistics play in ensuring evidence packages meet the expectations of multiple regulatory agencies?

Data generation, integrity and analysis sit at the centre of regulatory credibility. Across global development programs, it is not enough to collect large volumes of data; the evidence must be structured, analysable, and capable of supporting consistent interpretation across jurisdictions. Strong data governance ensures that the right data sets, endpoints, populations, methods are defined early to produce evidence that is both scientifically robust and regulator-ready.

Biostatisticians play a critical role in translating clinical objectives into decision-useful study designs. Their contribution will inform how variability is managed, how sample sizes are justified, how interim decisions are made, and how results will ultimately be interpreted. This becomes particularly important when Sponsors are trying to satisfy different multiple Regulatory Agencies, each of which may view benefit, risk, and evidentiary thresholds through a slightly different lens.

The strategic value is that well-designed evidence packages reduce uncertainty. They improve the consistency and interpretability of outcomes, strengthen sponsor credibility in regulatory interactions, and reduce the risk that a program is delayed by questions that could have been anticipated earlier. At board level, strong data strategy is not simply a technical function—it is a core driver of regulatory resilience and asset value.

In therapeutic areas like oncology, dermatology, and ophthalmology, what specific complexities are shaping early-phase clinical development today?

Early-phase development is becoming more complex because therapeutic areas now demand greater precision in both scientific design and operational execution. In many indications including oncology, dermatology, and ophthalmology alike, Sponsors are faced with complexity in patient needs, competition from other clinical studies but also the increase in approved medicines and the need to achieve outcomes that align with increasing regulatory scrutiny. 

In many oncology studies, the development of more precise medicines that are intended for biomarker-defined populations, the need for Sponsors to consider potential combination strategies, and evolving dose-optimisation expectations, and the need to balance speed with patient safety means that early phase studies need to be designed better and be able to evolve as new data comes through. Better design means better outcomes.

In other therapeutic areas such as ophthalmology and dermatology, the ability to maintain endpoint sensitivity, coupled with patient-reported outcomes, and the need to distinguish clinically meaningful benefit in diseases with heterogeneous presentation increases risk in study outcomes. In ophthalmic indications, the importance of preserving data quality where sample sizes may be limited, study designs are breaking new ground in the development of outcomes that support biological/pharmacological response confirmation before potential clinical sign and symptoms showing improved vision are reported. Sponsors may therefore achieve a successful outcome earlier, allowing greater confidence to expand patient inclusion and potentially preserving vision

The common theme across these areas is that early development can no longer rely on generic templates. Success increasingly depends on tailoring the protocol, endpoints, operational model, and data strategy to the realities of the disease area. For Sponsors, that means greater upfront planning—but also a better chance of generating evidence that is meaningful, credible, and strategically useful.