• Home
  • News
  • BIOE Ph.D. Graduate Secures TEDCO Funding to...

News Story

BIOE Ph.D. Graduate Secures TEDCO Funding to Advance Inflammatory Bowel Disease Therapeutics

Nicholas Pirolli, a recent Ph.D. graduate from the Fischell Department of Bioengineering (BIOE) at the University of Maryland, has secured funding from the Maryland Innovation Initiative (MII) through TEDCO to support the development of a novel therapeutic approach for inflammatory bowel disease (IBD) and similar inflammatory intestinal diseases. Pirolli’s graduate research, conducted under the mentorship of BIOE Associate Professor Steven Jay, centered on a technology that genetically programs probiotic bacteria to produce high yields of therapeutic extracellular vesicles (EVs), overcoming a critical hurdle in the development of this novel therapeutic method.

IBD affects around 3 million Americans and is associated with debilitating symptoms and an elevated risk of cancer, and the need for surgery. Current treatments have limited efficacy due to their inability to target key underlying causes of IBD, like mucosal wound healing, in addition to their high costs and specific safety concerns. Pirolli’s research addresses this by engineering Lactiplantibacillus plantarum, a Gram-positive probiotic bacteria, to produce bacterial extracellular vesicles (BEVs) that demonstrate strong therapeutic potential in preclinical mouse models. These biologic nanovesicles, which are a thousand times smaller than the bacteria themselves, can be administered orally to promote mucosal wound healing and modulate inflammation without the risks and limitations associated with live probiotic therapies and conventional IBD treatments.

Pirolli’s technology significantly boosts the production rate of BEVs around 70-fold without requiring specialized processes, skills, or equipment. This breakthrough, which overcomes a long-standing manufacturing bottleneck facing EV therapeutics, makes BEV-based therapies scalable and financially viable. A U.S. patent application has been filed through the University of Maryland, with additional patent applications planned worldwide. A second BEV technology has been disclosed to UM Ventures that allows for the production of engineered BEVs loaded with protein therapeutics, such as antibodies or peptides, and is expected to be patented as well.

“We invented a genetically based technology that essentially programs probiotic bacteria to produce 70 times as many BEVs and solves a critical regulatory hurdle in the development of BEV therapeutics.” Pirolli explained, “Without this technology, industrial biomanufacturing of BEV therapeutics presents major regulatory risks, as well as high costs that could limit possible applications of BEV therapeutics.” 

To evaluate clinical promise, Pirolli and his team tested the high-yield BEVs in a mouse model of colitis. Results showed the BEVs significantly reduced intestinal tissue damage and inflammation, with efficacy on par or better than current FDA-approved IBD treatments and live probiotics. This success laid the foundation for securing the TEDCO funding in his proposal. 

The momentum from this research has already led to the formation of Expora Therapeutics, a spin-off company dedicated to translating the laboratory technology into clinical applications. Although Expora Therapeutics was recently established, the current TEDCO funding is aimed at advancing university-based research and validating the underlying technology, while also providing support for planning the transition to the clinic. Plans for a second-phase MII application aimed at supporting the company's growth are already underway, with the team preparing to apply later this year in addition to Expora’s other efforts, fundraising, and meeting with the FDA. 

“Developing these skills is not traditionally emphasized in Ph.D. training. I had to teach myself and find a lot of people to learn from to understand the other 90 percent of what it takes to develop a therapeutic.”

-Nicholas Pirolli

Securing funding also required Pirolli to quickly become proficient in the non-scientific aspects of therapeutic development. Beyond proving scientific efficacy, he needed to understand how the therapy would fit into the healthcare ecosystem, its value to physicians and patients, and how to build a viable pathway toward clinical trials. Developing these skills, which are not traditionally emphasized in Ph.D. training, became a critical part of his success in securing TEDCO support.

“Developing these skills is not traditionally emphasized in Ph.D. training,” Pirolli said. “I had to teach myself and find a lot of people to learn from to understand the other 90 percent of what it takes to develop a therapeutic.”

Pirolli strengthened his commercialization strategy by building a network of advisors through the University of Maryland's regional and national I-Corps programs and the LifeX accelerator. These programs exposed him to a plethora of conversations with industry leaders, investors, and clinical experts, providing the insight necessary to craft a competitive funding proposal. Through this extensive mentorship network, he was able to translate complex technical details into a compelling vision for product development and commercialization.

The support extended across multiple disciplines. Clinical insights were provided by Dr. Jean-Pierre Raufman, Division Head and Professor of Gastroenterology at the University of Maryland Medical School (UMSOM). Robert E. Fischell Distinguished Professor and Director of the Fischell Institute for Biomedical Devices, William Bentley, contributed knowledge in bacterial genetic engineering in addition to his prior role as co-advisor for Pirolli’s thesis. Robert Vandenberg, who advises faculty on TEDCO MII applications, and LifeX played a critical role in refining the project’s milestones and preparing regulatory strategies. Together, this cross-functional team provided the guidance needed to advance the project beyond the laboratory.

Despite the strong support network, navigating the commercialization process posed challenges. Receiving expert advice from multiple qualified individuals often resulted in conflicting perspectives, forcing Pirolli to carefully weigh options and make strategic decisions about the project's direction. Balancing these opinions was essential to maintaining progress while staying true to the project's long-term goals.

The TEDCO grant has accelerated the team's ability to move the technology closer to clinical reality. With the foundation built through university research, the team is now exploring the best immediate application of the technology, including a highly promising approach to prevent death of preterm infants from an untreatable intestinal disease known as necrotizing enterocolitis (NEC). This flexibility in application reflects the broader therapeutic potential of their BEV platform technologies.

Looking to the future, Pirolli aims to advance the therapeutic technology into human clinical trials and realize the potential of BEV therapeutics to transform the way gastrointestinal diseases are managed. He focuses on bringing this innovation to patients, with a strong commitment to continuing the translational work he began during his time at the University of Maryland.

The mentorship and environment within Professor Steven Jay’s lab proved to be a crucial part of Pirolli’s success. “Through his mentorship, he's completely changed my life,” Pirolli said. “He was willing to allow me to take the reins, so to speak, and put his trust in me. I really respected that.”


Published April 29, 2025