Lymphatic Targeting - Lipid Transport

Therapeutic strategies for immunomodulation by targeting the mesenteric lymph nodes


Lipid prodrug technology designed to utilize natural lipid transport system to enable lymphatic targeting

PureTech is developing a lymphatic targeting approach that leverages the body’s natural lipid transport mechanisms to substantially enhance the transport of compounds into the lymphatic system from an oral route. Nearly all dietary lipids (such as triglycerides) are absorbed from the small intestine into lymphatic vessels (lacteals), and these vessels transport lipids and immune cells to the mesenteric lymph nodes in the gut before entering systemic circulation. To access this absorption pathway, a triglyceride is reversibly attached to a drug of interest via a linker optimized to release the drug at the site of interest.

We are advancing a broad pipeline of programs to treat cognitive deficiency and improve symptoms associated with medical conditions across neurology and psychiatry, including attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), autism spectrum disorder (ASD), multiple sclerosis (MS) and various other neuroinflammatory diseases. We are also developing associated clinical monitors and measurement-based care applications. Our lead, patented technology platform is exclusively licensed from the lab of Dr. Adam Gazzaley at the University of California, San Francisco (UCSF), and augmented by proprietary adaptive algorithms developed by our team.

  • Our Approach
    • An additional advantage of the lymphatic transport strategy is that uptake of the drug into the lymphatic system avoids “first pass metabolism” of the drug by the liver. One of the liver’s key functions is to break down certain compounds, and this can severely limit how much of some drugs survive the journey from the stomach to the main circulatory system. 
    • This platform has been optimized to enable the therapeutic to integrate into the body’s natural lipid absorption pathways and subsequently be released at the site of interest. Relative to other approaches using more simplistic hydrophobic modifications, the PureTech Health platform demonstrates one to two orders of magnitude improvement in lymphatic transport and target location exposure. This was achieved by re-imagining the therapeutic to include actual dietary lipid components – triglycerides – to more closely integrate within the natural lipid absorption pathway.
    • PureTech has successfully extended the lymphatic targeting platform to encompass more than twenty potential drugs as well as a range of new linker chemistries, which have demonstrated promising lymphatic targeting in preclinical studies, frequently directing above 20 percent of the orally administered dose into the lymph. Successful pharmacokinetic studies in large animals are supportive of translation of this technology into higher species.
  • Intellectual Property
    • PureTech has broad intellectual property coverage for this technology, currently owning or having exclusive rights to twenty nine (29) patent applications in seven (7) families of patent filings that are licensed from Monash University, which intellectual property is directed to compositions of matter, methods of use, and methods of treatment that cover classes of pro-drugs as well as the broad platform technologies.
  • Collaborations
    • In the April 2019, PureTech entered into a partnership with Boehringer Ingelheim (BI) to advance BI’s immunooncology product candidates using PureTech’s lymphatic targeting platform. Under the terms of the agreement, PureTech will receive up to $26 million, including upfront payments, research support, and preclinical milestones, and is eligible to receive more than $200 million in development and sales milestones, in addition to royalties on product sales.

An important benefit of the lymphatic trafficking route is the potential ability to target the mesenteric lymph nodes, as 70 percent of the body’s immune cells are found in these lymph nodes. PureTech’s approach is to manipulate the body’s immune “headquarters” through the gut, via an orally-administered treatment.