One Drug, Three Indications: How Small ClinOps Teams Manage Multi-Trial Execution

By Maureen Higgins, Ph.D., MBA, vice president, head of clinical operations, Step Pharma

In drug development, size is often equated with operational capability: Larger pipelines, bigger teams, and global infrastructure lead to a higher chance of success. But emerging biotechs, which account for an increasing proportion of innovative drug approvals (GlobalData), often go against this grain. Some of the most ambitious clinical development programs are being delivered by lean, tightly connected teams.

That is certainly true for our team at Step Pharma. Our clinical operations group consists of three people.

Yet, we are simultaneously running three clinical programs in a pipeline-in-a-product strategy for dencatistat, our first-in-class CTPS1 (cytidine triphosphate synthase 1) inhibitor. CTPS1 is a critical enzyme in pyrimidine nucleotide biosynthesis. By disrupting this single essential metabolic node, we offer a precision approach to treat diverse conditions through one well-validated target. This led us to clinical studies in lymphoma, solid tumors, and essential thrombocythemia (ET), with each indication presenting its own unique challenges in trial designs, regulatory paths, and patient populations. Having the same number of clinical programs as team members might sound impossible on paper, but it has become one of our biggest strengths.

The Importance Of Team Culture

In a small biotech, the success or failure of a program often comes down to the people running it. Trust and mutual respect, on top of expertise, are essential characteristics that keep a small organization moving.

At Step Pharma, everyone in the clinical operations team carries significant responsibility, but they also have a lot of autonomy. We rely on open communication, shared ownership, and the understanding that every decision affects the whole.

This means being deliberate about a potential team member’s fit. In small teams, one misalignment in attitude or communication can ripple through the entire operation. This doesn’t mean that someone isn’t well qualified or capable, but their experience may be better suited to a larger, more process-driven organization. Conversely, the right addition who aligns well with a company’s culture can be transformative. Individuals who thrive on collaboration and curiosity, who are comfortable in ambiguity and change, and who see figuring it out as part of the job are ideally suited for a small biotech.

Cross-Fertilization And Flexibility

With three programs in motion, we can’t afford silos. While each of us leads a particular program, there is constant cross-pollination in reviewing clinical data, managing vendor deliverables, and handling regulatory submissions. Every team member understands each study well enough to fully step in when needed. A program can’t stop for two weeks when someone goes on holiday.

This overlap creates resilience, builds trust, and makes us better decision makers. The insights we gain from one indication, whether a protocol nuance, an operational bottleneck, or an unexpected pharmacodynamic signal, feed directly into the others and provide benefits across all of the programs.

Having that visibility across programs means we can act quickly. When emerging data from the lymphoma study identified a dose-dependent reduction in platelets with dencatistat treatment, a cross-functional review of these findings enabled the program to expand very quickly to explore its potential therapeutic relevance in essential thrombocythemia (ET), a rare clonal blood disorder where platelet levels are raised. Developing a mechanistic understanding of the effect on platelets in a matter of months combined with the excellent safety profile seen in lymphoma patients was key to committing to the ET study. This cross-functional adaptability has defined our journey with dencatistat: Each step has been guided by data.

Our team also bridges clinical operations and disease biology, ensuring that operational decisions are informed by scientific rationale developed in collaboration with clinical and translational experts. Understanding why a study is structured a certain way is critical and allows for smarter decisions. When you’re working with a mechanism as novel as CTPS1 inhibition, the science itself is evolving alongside the clinical data. Operational decisions must therefore be made with scientific awareness.

Patient And Advocacy Group Engagement

When I began working in clinical research, involving patients in trial design or the development of patient-facing materials was rarely, if ever, considered. Today, three decades later, the active involvement of patient advocacy groups (PAGs), especially early in the development pathway, has positively impacted how we design and deliver clinical trials, creating tangible benefits for patients, investigators, and sponsors alike.

However, impact is not just about intent, it is about how we engage. Smaller, empowered, and focused teams such as ours are often better positioned to act on feedback in real time than larger, more complex operational structures. We worked with a PAG to rapidly refine informed consent language and other patient-facing documents to be more meaningful and respectful, thereby improving understanding and supporting fully-informed decision making. We heard from ET patients, the majority of whom are elderly, about their lived experience. This allowed us to better understand local/regional barriers to participation and proactively address practical challenges such as travel (and how that changes during the winter), caregiving, and home visit support.  The output from these cross-functional discussionswere implemented without layers of approval to slow the progress. This active listening and responsiveness has helped build authentic, trusting relationships with the PAGs, which, in the long term, supports patient recruitment and retention.  Equally important is the recognition that patient experience is not uniform, and we have engaged with advocacy groups in each country where our trial is active to better understand there can be significant variability in symptom burden, standards of care, geographic access, cultural context, and site capability. A one-size-fits-all approach risks oversimplification and missed opportunities, e.g. the needs of an elderly patient in the UK in the winter months are different than another inSpain.

Building Strong Vendor Relationships

For small teams, outsourcing is unavoidable to conserve costs, but choosing the right vendors makes all the difference.

We’ve worked hard to replace the traditional sponsor–vendor dynamic with something more open and collaborative with our CROs. When challenges arise, we tackle them together. This joint accountability is essential when resources are stretched and timelines are tight.

We’ve deliberately partnered with a midsize CRO for our program as they are typically more flexible, faster to adapt, and more aligned with how small biotechs operate.

As with our own team, people culture is key; we invest time in building rapport with project managers, monitors, and regulatory specialists, ensuring that communication is consistent. We hold regular reviews at which we discuss metrics, but we also qualitatively address what’s working, what isn’t, and what can be improved. That open dialogue has allowed us to navigate challenges proactively, from site activation delays to protocol amendments, and to focus effort where it is needed without losing momentum.

Navigating Regulatory Complexity

Running three programs means navigating multiple regulatory frameworks and timelines. A consistent, tight-knit team, plus continuity with the same CRO and regulatory leads across studies, has created valuable efficiencies. We’ve been able to maintain consistent documentation standards and retain institutional memory across submissions. And with dencatistat receiving Orphan Drug designation in T cell lymphoma, learnings from that process could be carried into our future indications.

As the regulatory landscape evolves, we have learned to anticipate change rather than react to it. Our team routinely integrates new requirements or feedback into our next submission. With a novel first-in-class drug, we’re often operating in uncharted territory. Each regulatory interaction teaches us something new, and those learnings immediately inform how we approach the next. The ability to adapt protocols, documents, and processes quickly has been central to keeping all three programs moving in parallel.

Conclusion

Delivering three clinical programs with a three-person team is not about squeezing more work out of fewer people, it’s about approaching the work differently. At Step Pharma, we’ve learned that success in a lean environment depends on three things above all: a strong, respectful culture based in trust; strong partnerships with vendors and investigators; and a willingness to adapt as the science and data evolve.

About The Author:

Maureen Higgins, Ph.D., MBA, has over 30 years of experience in global clinical research across pharmaceutical, biotech, and CRO settings.  She has led international development programs from early-phase studies through to marketing authorization across therapeutic areas including oncology, infectious disease, and women’s health, and provided consultancy to a range of biopharmaceutical companies.  Throughout her career, she has worked with global regulators, including the FDA and European authorities, guiding cross-functional teams through complex and evolving environments. She is motivated about advancing clinical operations and contributing to the development of treatments that make a meaningful difference for patients.