Laguna Biotherapeutics, Inc. (Laguna), a clinical-stage biotechnology company focused on novel live bacterial therapeutics, today announced the publication of foundational preclinical research in the Proceedings of the National Academy of Sciences (PNAS). The peer-reviewed study demonstrates that genetically engineering Listeria monocytogenes (L. monocytogenes) produce riboflavin that drives a robust mucosal-associated invariant T (MAIT) cell response, yielding potent efficacy in both infectious disease and oncology models.

The paper, titled "Avoidance of MAIT cells is an essential determinant of Listeria monocytogenes pathogenesis", elucidates how wild-type L. monocytogenes naturally evades MAIT cells - a highly conserved and abundant population of innate-like T cells - by lacking the riboflavin biosynthetic pathway. The researchers demonstrated that, by restoring this pathway, the engineered strain (L. monocytogenes-ribDEAHT) becomes fully attenuated in wild-type models while prompting rapid and robust MAIT cell expansion.

Crucially, the study showed that therapeutic administration of this engineered Listeria provided robust protection against the respiratory pathogen Francisella tularensis and significantly inhibited tumor growth, demonstrating efficacy even in the absence of traditional CD8+ T cells.

"This publication provides powerful validation for our core scientific thesis: by rationally engineering the mechanisms Listeria uses to interact with the human immune system, we can unlock highly specific, durable, and potent immune responses," said Jonathan Kotula, Ph.D., CEO and co-founder of Laguna. "The ability to selectively activate MAIT cells to attack tumors and clear intracellular pathogens without relying entirely on CD8+ T cells represents a significant paradigm shift. It broadens the horizon for our platform and reinforces our commitment to developing systems-level immunotherapies for patients facing complex diseases."

The findings reinforce the versatility of Laguna's approach to modulating innate T cells, demonstrating that rationally designed live bacterial vectors can be directed to harness distinct immunological pathways, such as MAIT cells, to overcome the limitations of current therapeutic modalities in cancer and infectious diseases.

The full manuscript is available online in the June 16, 2026, issue of PNAS (DOI: 10.1073/pnas.2601925123).

About Laguna Biotherapeutics, Inc. (Laguna)

Laguna is a privately funded, clinical-stage biotechnology company headquartered in San Francisco, CA with research labs in Siena, Italy. It is focused on developing novel therapeutics that leverage Lm to activate and expand the immune system to create impactful treatments across oncology, as well as inflammatory and infectious disease.