Direct Biologics

Kevin Hicok is Vice President of R&D at Direct Biologics, where he leads research and development programming for an emerging therapeutic modality based on an extracellular vesicle-enriched secretome. Drawing on more than 30 years in cell science, he brings experience across cell agriculture, regenerative cell technology and biologics development to guide research strategy, scientific programs and team leadership.

Building a Path for a New Therapeutic Modality

Developing a new class of medicine requires more than applying established methods to an unfamiliar product. It demands new ways of thinking when the scientific and development standards that normally guide R&D do not yet exist. For Hicok, leading research in this environment means addressing questions that have no established answers while maintaining the rigor required to demonstrate safety and efficacy. The challenge is particularly pronounced when a therapeutic contains thousands of different biomolecules, making conventional approaches to establishing identity, purity and potency difficult to apply.

That reality has made creativity and persistence central to Hicok’s approach to R&D leadership. Rather than treating uncertainty as a reason to pause, he encourages the team to work through unfamiliar problems and develop solutions as the science progresses. The approach has become increasingly important as Direct Biologics moves into Phase III trials, where pioneering work must meet the demands of later-stage clinical development.

Choosing Where Science Can Make a Difference

A broad biological platform can create an unusual strategic problem. If a therapeutic can interact with multiple biological pathways and potentially regulate immune function across different disease states, the number of possible applications can quickly outgrow the resources available to investigate them.

“ R&D leaders have to remain willing to examine whether the mechanism originally proposed for a therapy still explains the observed biological effects. “

Direct Biologics has addressed that challenge by maintaining a disciplined approach to indication selection. Instead of pursuing every disease that might respond to its platform, the R&D team draws on roughly three decades of cell biology data associated with its human bone marrow-derived mesenchymal stem stromal cell source. That historical foundation helps identify areas where the underlying biology offers a credible basis for further investigation.

AI analytics adds another layer to that process by helping researchers identify disease areas that warrant closer attention. The resulting candidates are then evaluated against practical considerations, including the level of clinical need and whether an investigation can produce clear clinical endpoints.

This approach has helped Direct Biologics concentrate its efforts on conditions such as ARDS, ulcerative colitis and Crohn’s disease, where relevant biological characteristics provide a rationale for continued research. The discipline lies in deciding where the science deserves deeper investment before resources become diluted across too many possibilities.

Designing Manufacturing Around Biological Complexity

Once a promising therapeutic direction has been identified, another challenge emerges. A complex biological product must retain a consistent profile as development moves from laboratory research toward clinical manufacturing.

Hicok considers an understanding of the therapeutic cell source one of the most underestimated elements of that transition. Mesenchymal stem stromal cells respond continuously to changes in their surrounding environment. They can switch genes on and off according to those conditions, which can alter the composition of the secretome they produce.

That biological responsiveness creates a manufacturing challenge. Two cell cultures operating under apparently similar conditions can produce meaningfully different outputs, particularly as processes are scaled. Recognizing that variability early has allowed Direct Biologics to build manufacturing processes and controls that account for those influences rather than discovering them late in development.

Hicok also advocates conducting several manufacturing runs at a commercially relevant scale before development has progressed too far. Early scale-up work can reveal differences between laboratory and larger-scale production while there is still time to address them. For complex biologics, understanding those differences early can prevent manufacturing assumptions from becoming development constraints later.

Studying Biology Before Trying to Redesign It

Direct Biologics’ natural intelligence approach reflects another deliberate choice in its R&D model. Instead of immediately attempting to redesign biological systems through genetic or protein engineering, the company first seeks to understand how naturally derived biological components behave.

The premise is straightforward. Biological systems have evolved to respond to injury and maintain normal function. Studying those responses can therefore provide useful information about how naturally occurring secretome components interact with human cells, organs and tissue-based systems.

Inside the R&D organization, that philosophy translates into a direct study of those biological interactions. Researchers examine how the naturally derived secretome interacts with human cells, organs and tissue-based systems to better understand the biological responses involved.

“ The discipline lies in deciding where the science deserves deeper investment before resources become diluted across too many possibilities. “

The approach also reflects Hicok’s preference for simplifying complex problems before adding layers of intervention. Direct Biologics first asks what can be learned from the system before introducing additional layers of complexity or attempting to alter it.

Knowing When the Original Hypothesis Is No Longer Enough

The history of mesenchymal stem stromal cell research provides a clear example of how scientific assumptions can shape development strategies. Early work showed that these cells could be coaxed in laboratory conditions to behave like mature cell types such as fat, cartilage, bone and neurons. That led researchers to view them as an adult counterpart to embryonic stem cells, and companies built development strategies around the expectation that the cells would become replacement tissue in patients.

Later research showed that the cells were not implanting and transforming into new tissue in the way initially expected. Attention increasingly shifted toward the cell secretome and its role in producing biological effects in vivo.

For Hicok, the lesson extends beyond that particular field. R&D leaders have to remain willing to examine whether the mechanism originally proposed for a therapy still explains the observed biological effects. That means asking whether the biological effect can be characterized and controlled, whether the resulting product can be manufactured consistently and whether the proposed mechanism connects meaningfully to patient outcomes.

Scientific leadership therefore, requires a willingness to let evidence alter the development story itself. Preserving an original hypothesis simply because it has shaped a company’s identity or attracted investment can prevent researchers from recognizing a more accurate explanation of how a therapy works.

From Doing Science to Enabling Scientists

Moving into R&D leadership requires scientists to apply that same adaptability to their own roles. Technical expertise remains important, but leadership requires a broader set of capabilities.

Hicok emphasizes the importance of communication and people skills because R&D leaders increasingly serve as scientific translators across an organization. Their work has to connect with quality, regulatory and clinical functions and eventually with teams responsible for bringing a therapy to the market.

That shift also requires scientists to relinquish some direct control over the work they once performed themselves. Hicok describes this transition as “giving your pipette away,” a difficult adjustment for researchers who have built their careers around personally solving scientific problems.

The reward comes from seeing a capable team take ownership of that work. Once researchers have the confidence and resources to execute independently, the leader’s role changes from performing the science to creating the conditions in which others can advance it.

For Direct Biologics, that distinction carries particular weight as its programs move deeper into clinical development. Advancing an emerging therapeutic modality requires scientific rigor, but sustaining that progress also depends on developing people who can take greater ownership of complex programs.

For Direct Biologics, that distinction carries particular weight as its programs move deeper into clinical development. Advancing an emerging therapeutic modality requires scientific rigor, but sustaining that progress also depends on developing people who can take greater ownership of complex programs.