Driving Towards Execution – From Theory to Application

As we approach Biocom’s 16^th annual Global Partnering & Investor Conference, we sat down with Carolina Ahrendt, Principal Consultant in Program Leadership at Halloran, and Monika Swietlicka, Principal Consultant in Regulatory Affairs at Halloran, to build upon the first part in the content series, “Biotech After the Reset: Capital, Discipline, and Return of Execution.”

Expectations around execution were a major theme at the J.P. Morgan Healthcare Conference, and in particular, execution is what investors are focusing on. But what exactly does that mean and look like?

Carolina and Monika share their point of view and recommendations on how to turn the notion of execution into a reality.

Q: Many speakers and investors at J.P. Morgan noted there is a tightened focus on execution. Since Biocom’s Global Partnering & Investor Conference is a natural continuation of the post J.P. Morgan dialogue, we anticipate similar conversation to come. So, what does execution signal and mean to you?

Carolina:

I recently watched F1: The Movie and noticed the corollary to drug development.

It takes a pit crew – a team of experts – to guide companies to success. Today, even more, success looks like pulling the thread from strategy to strong tactical planning supported by the right people and processes in place. Execution is about how companies operate internally to move development forward.

I’ve worked with many small and mid-sized biotechs, transforming them from a fragmented organization to an integrated unit propelled by proper planning, communication, collaboration, and high performance to enable a relentless focus on execution that enables success. Often, companies need a proponent on the team to keep the foot on the execution pedal – one that knows the strategy, the challenges, and can make informed, disciplined decisions while still reaching alignment with the necessary stakeholders and achieving their drug development goals.

This ‘show me’ approach includes companies who demonstrate that they can operate efficiently within a lean team, create tangible value by achieving key development milestones outlined in their drug development roadmap (IND, clinical data, etc.), and deliver on their promises that go beyond scientific vision or strategy.

Essentially, investors are looking for that Grand Prix drug development roadmap with the right pit crew to support every turn, blending experiences to show they can deliver and capitalize on technology to create efficiencies.

Monika:

I agree with Carolina – execution is the ability to translate strategy into outcomes – and in the current environment, it also signals something very specific: regulatory durability and capital efficiency. Investors are no longer evaluating whether a program has a plan; they are evaluating whether that plan will remain viable as regulatory expectations, evidentiary standards, and policy continue to evolve.

Over the past year, a series of regulatory decisions and policy updates, particularly in rare disease and advanced therapies, have underscored that the evidentiary bar continues to evolve. While these shifts are refining approval standards, they are also increasing the importance of integrated development planning, scalable manufacturing, and clinically meaningful endpoints. In this environment, execution has become a central differentiator for both operators and investors navigating capital allocation and partnership decisions.

That means a development strategy cannot be point-in-time credible; it must be resilient at submission. We are seeing clear examples where programs aligned on accelerated, single arm approaches early in development were later declined because the standard for clinical meaningfulness, durability, or interpretability increased. Execution, therefore, requires continuous re-benchmarking against recent regulatory decisions and designing programs with built-in optionality rather than relying on historical precedent.

Execution also requires integrating functions earlier than many organizations are structured to do. Endpoint strategies that support approval do not always support reimbursement. If commercial, access, and HEOR perspectives are not incorporated before Phase 3 design, companies risk achieving an approvable label that does not translate into adoption – something investors now view as a fundamental execution gap.

From an investor lens, execution signals an integrated development narrative: a plan that remains viable under evolving regulatory expectations, evidence that supports both approval and access, manufacturing that can scale without reset, and clearly defined decision gates tied to value inflection points. It is the ability to move from early signal to approvable and adoptable product without requiring a late-stage strategic pivot.

That level of forward planning is what differentiates scientific promise from a deliverable asset.

Q: What are specific, positive execution examples that come to mind? Any lessons gleaned from those?

Carolina:

• Build a credible regulatory strategy: In early-stage development, I think that building a regulatory strategy is important because you want to build a collaborative relationship with the Agency, showcase you understand the regulatory precedence, and can navigate the interpretation of changing guidance while concurrently meeting the company’s drug development program goals.

The strategy starts with asking questions: What do we want to discuss with the Agency and why? How can we prevent a clinical hold? How can we capitalize on special designations for this patient population? What have others done in this space based on the summary basis of approval? What are regulatory tools to accelerate development?

By answering these big picture concepts early on, it will help to strengthen your position statements for a Pre-IND meeting package which is usually your first entry point in interacting with the FDA. Then, as you move through development, you’ll continuously evaluate, adjust, and potentially alter your regulatory strategy pending FDA feedback and clinical data. Each steppingstone or stage gate means evaluating your regulatory strategy. Therefore, I think of strategy of evaluating your options, figuring out the best way to de-risk the program, and adapting it along the way.

• Ensure proper program/project management to move from strategy to execution: Once the program and regulatory strategy have been defined, the second question I always receive from clients I support is ‘what are the timelines and resources needed to make this happen?’ Followed by ‘how quickly can we make this happen?’

Creating integrated drug development timelines is a team sport and allows execution to happen more seamlessly and with fewer problems. The questions in the execution phase include the following: What are we trying to do (create a meeting package, submit an IND, submit an NDA or BLA)? Do we have all the resources for the assigned tasks needed to execute (CMC, Clinical, Nonclinical, Regulatory)? Do we have organized processes in place so people can locate information, write based upon source documents, and enable version control? Is there a governance model with an escalation plan to escalate risks with mitigation plans to make informed decisions?

If everyone is aligned on the strategy, timelines, assignments, and ways of working, execution becomes easier. This is the power of program/project management.

This reminds me, again, of F1: The Movie. While drivers set the tone, they communicate mid-race with their team to make split-second decisions that can make or break a race. Strong team relationships align with the strategy early on, turn data into performance gains, and work together to fine-tune where needed to push the team forward.

• Build quality in earlier into the drug development journey: If companies build and plan for quality in their processes early on, it helps throughout drug development and especially for future inspections by the FDA as companies think about moving towards commercialization.

For example, quality is multi-faceted because it covers CMC manufacturing (GMP), clinical study operations (GCP), and nonclinical study conduct (GLP). Standard operating procedures are there to validate consistency in process, common understanding of roles and responsibilities, and proper documentation. This helps to de-risk issues especially when something goes wrong and internal investigation is done to find the root cause. A procedure for corrective and preventative actions enables a mechanism for escalating and resolving issues – don’t overlook that.

By building these quality plans, systems and audits along the way, you help to save time and efficiencies when an FDA (or another Agency) Inspector shows up at your door. As a bonus, it helps when you are doing due diligence because you can demonstrate to potential partners that you know how to execute while concurrently imparting quality checks along development.

Monika:

I agree with Carolina. When strategy, program management, and quality systems are established early, execution becomes more predictable. You see that foundation in how teams prepare for agency interactions, document decisions, and manage risk. In my experience, the impact of that work becomes most visible at key development inflection points, where planning is translated into operational progress.

• IND as the first operational catalyst: This is where early scientific, regulatory, and CMC planning comes together in a protocol that enables dosing. Programs that reach IND with aligned dose rationale, a phase-appropriate manufacturing process, and a well-structured clinical design are often able to generate interpretable early data on schedule, establishing regulatory credibility and an initial value inflection point.
• End-of-Phase 2 as the alignment milestone: The benefits of integrated planning are especially clear at End-of-Phase 2. When endpoint strategy, statistical design, and manufacturing approach are aligned and informed by agency feedback, teams can enter pivotal development with greater clarity and fewer structural changes. This helps preserve both timeline and capital while maintaining development momentum.
• Pre-BLA as the continuity point: Carolina’s emphasis on building quality early is reflected in the transition to submission. Organizations that have treated CMC, data integrity, and quality governance as critical path activities throughout development are often able to move from last-patient-last-visit to BLA in a more streamlined way, with fewer new questions introduced late in the process. That continuity at the point of submission is a strong positive execution signal.

Lessons learned: Across these milestones, execution is demonstrated by continuity and integration. When IND readiness reflects earlier regulatory thinking, End-of-Phase 2 confirms the pivotal path, and the BLA compiles decisions made over time, programs maintain momentum and reduce the need for late-stage adjustments, ultimately supporting more predictable timelines and earlier patient access.

Reaching the Finishing Line

It’s going to take the right crew, the right strategy, and the right processes and systems to go from vision to execution – and the ability to adapt as the track evolves. Recent regulatory decisions and shifting evidentiary expectations reinforce finishing strong requires development pathways that are resilient to change, with evidence, manufacturing, and quality strategies designed to withstand review without late-stage resets.

F1 drivers know this well – it’s not about who starts fast, but about who finishes strong. And it certainly takes a relentlessly focused team, not just the driver, to win.

We look forward to continuing the conversation at Biocom’s Global Partnering and Investor conference.

Halloran Consulting Group, part of ProductLife Group (PLG), partners with early-stage companies, CEOs, and investors to bring deep regulatory and development expertise with global reach, helping teams execute with discipline across critical inflection points.

Contributing authors: