The Wyss Institute at Harvard University announced today that Ropirio Therapeutics, Inc. (Ropirio) has secured a worldwide, exclusive license from Harvard's Office of Technology Development (OTD) and Boston University (BU)'s Technology Development office for novel molecules that activate the lymphatic system - a first in the pharma industry.
There has been a tremendous amount of research into the lymphatic system over the last decade, with scientists uncovering new lymphatic vasculature and understanding the critical role it plays across a wide range of serious diseases. Ropirio is building on this explosion of research and will be the first company to develop therapeutics that specifically target and activate the lymphatic system, enabling the treatment of a multitude of serious diseases."
Jerald Korn, CEO of Ropirio
Ropirio's assets include a pioneering in vitro platform that models human lymphatic vessels, as well as a stable of proprietary small molecules that modulate specific targets within lymphatic cells.
The human body's lymphatic system is extensive and complex. It comprises a network of vessels that collect and transport fluids throughout the body. This system is also a major conduit for immune cells, and thus critical for healthy immune responses.
Work conducted in the lab of Wyss Core Faculty member Chris Chen, M.D., Ph.D. led to the creation of a lymphatic vessel -on-a-chip that accurately models human lymphatics in a microfluidic in vitro system. The 3D model consists of two tiny channels suspended in a collagen matrix: one lined with human lymphatic cells to form a vessel, the other perfused with a surrogate lymph fluid composed of molecules including fatty acids, phospholipids, albumin, and insoluble particles. By pressurizing the fluid channel, the researchers were able to replicate the process by which fluid from around the body's tissues drains into lymph vessels.
Chen's team discovered that the addition of inflammatory cytokines to their lymphatic vessel chip significantly reduced lymphatic drainage, mimicking human response to inflammation. Building on this finding, the team identified a druggable pathway that can activate lymphatics by opening junctions between lymphatic endothelial cells and restoring normal drainage, even in the setting of inflammation. This biology is specific to lymphatic tissues, allowing for selective activation of drainage without causing side effects in other parts of the body.
"Our work in the lab revealed just how critical it is to understand the molecular underpinnings of human biology in order to create effective treatments for diseases. Prior to this research, it was thought that lymphatic vessels drained fluid passively, but we demonstrated that lymphatics respond actively to external factors, opening cell-cell junctions in response to fluid and closing these junctions in the face of inflammation. We were also able to demonstrate that by inhibiting a target, we could restore lymphatic drainage even in the presence of inflammation," said Chen, who is also the William Fairfield Warren Distinguished Professor of Biomedical Engineering and Director of the Biological Design Center at BU.
Following this breakthrough discovery, a team at the Wyss Institute comprising industry veterans Ken Carlson, Ph.D., Joel Moore, Ph.D., and Sylvie Bernier, Ph.D coalesced in order to translate this biological result into a tangible human therapeutic. The group rapidly assembled a complete drug discovery platform that ultimately produced potent, orally bioavailable compounds that demonstrated efficacy in the gold-standard animal model for secondary lymphedema. "This program exemplified the collaborative power of the Wyss Institute's translational engine through its transformation of fundamental biological science into the foundation of Ropirio Therapeutics," said Moore, who now serves as the SVP of Non-Clinical Development at Ropirio.
Ropirio was founded by Chen along with fellow Wyss Faculty member Sangeeta Bhatia, M.D., Ph.D., who is also the John J. and Dorothy Wilson Professor at MIT's Institute for Medical Engineering and Science and Electrical Engineering and Computer Science; Rene Russo, Pharm.D., Chief Executive Officer of Xilio Therapeutics; and Joel Moore, Ph.D., SVP of Non-Clinical Development at Ropirio and Medicinal Chemist at the Wyss Institute. Ropirio's portfolio includes several small molecule drugs targeting the lymphatic system, which it aims to start testing in clinical trials in 2026.
"It has been exhilarating to see how quickly the Ropirio team progressed from an idea in the lab to a set of potentially revolutionary treatments for the lymphatic system by combining forefront science with an experienced team of drug developers at the Institute," said Wyss Founding Director and Core Faculty member Don Ingber, M.D., Ph.D. "They are a model example of the Wyss Institute's commitment to accelerating impactful technologies to the market, and we are lucky to count them among our outstanding community of Lumineers." Ingber is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children's Hospital and the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.
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