GlyphTM Technology Platform

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GlyphTM Technology Platform
Orphan & other
neurological indications

A synthetic lymphatic targeting chemistry platform being developed to employ the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system by (1) targeting the mesenteric lymph nodes and (2) bypassing first-pass metabolism.

Phase completedPhase in progress
Lymphatic targeting chemistry platform leveraging absorption of dietary lipids to traffic therapeutics via the lymphatic system

PureTech is developing a synthetic lymphatic-targeting chemistry platform called GlyphTM, which employs the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system. Consumed nutrients and orally-administered pharmaceuticals are initially absorbed by the small intestine mucosa, distributed to the liver by the portal vein before entering systemic circulation.

Importantly, many consumed dietary lipids, particularly triglycerides, enter systemic circulation by an alternate route. Triglycerides, which are composed of three fatty acid chains tethered to a 3-carbon glycerol molecule, are absorbed by small intestine mucosal enterocytes where they are incorporated into large lipid-protein complexes, or chylomicrons, and released into the submucosa. Chylomicrons are too large to enter blood vessels and are instead taken up by submucosal lymphatic vessels. Once in the lymphatic vessels, they are transported to mesenteric lymph nodes associated with the GI tract where they pass into larger lymphatic sinuses connected to the thoracic duct, then transition to systemic circulation. This is in contrast to conventional systemic circulation via the gut and liver.

  • Innovative Approach to Solving the Problem
    • PureTech believes its Glyph technology platform provides the following capabilities:
      • Targeting the mesenteric lymph nodes:
        • This lymphatic targeting technology has important features potentially offering meaningful advantages in the creation of orally-administered medicines, especially those that need to reach immune system drug targets present in the GI tract mucosa and submucosa, such as intestine-associated immune cells, or in the mesenteric lymphatic vasculature, such as circulating immune cells, and mesenteric lymph nodes, such as lymph node stromal cells, antigen presenting DCs and lymph node-associated immune cells.
      • Enhancing oral bio-availability by bypassing first-pass metabolism:
        • PureTech believes this technology could provide a broadly applicable modular means to significantly enhance the bioavailability of orally-administered drugs that suffer from substantial first-pass liver metabolism or those drugs, especially those utilized in drug combination therapies, that act as modulators (inducers and/or inhibitors) of drug-metabolizing systems in the liver.
    • PureTech's proprietary Glyph technology platform takes advantage of the fact that one of the triglyceride-associated fatty acids remains bound to dietary lipids during intestinal absorption, chylomicron conversion, lymphatic vessel uptake and eventual transport into the circulatory system. Using a modular set of proprietary chemical entities, small molecule pharmaceutical compounds can be docked to triglycerides where, following oral administration, the small molecule is directed into the mesenteric lymphatic system and on to systemic circulation. The point of original small molecule release from the triglyceride is governed by self-cleaving chemical structures, with different release-timing features, that tether the small molecule to the module connected to the triglyceride.
  • Milestones Achieved
    • PureTech has successfully extended its lymphatic targeting platform to encompass more than 20 molecules as well as a range of novel linker chemistries that have demonstrated promising lymphatic targeting in preclinical studies. PureTech expects to select product candidates from this and ongoing discovery work.
    • In April 2019, PureTech announced an alliance with Boehringer Ingelheim, which is initially focused on evaluating the feasibility of applying the Company's Glyph technology platform to one of its immuno-oncology product candidates.
  • Intellectual Property
    • PureTech has broad intellectual property coverage for its proprietary Glyph technology platform, which includes exclusively licensed and co-owned patent applications, as well as company-owned patent applications. These patent applications cover compositions of matter, methods of use and methods of treatment encompassing specific chemical modifications, including a wide range of novel linker chemistries, as well as various classes of lymphatic targeting therapeutics, which include prodrugs for a large number of APIs, for use in the treatment of a wide range of diseases and disorders. The most advanced of these is LYT-300, which is an oral form of FDA-approved allopregnanolone, a natural neurosteroid, that may be applicable to a range of neurological conditions.
    • As of June 30, 2020, PureTech's Glyph technology platform IP portfolio consists of 19 patent families comprising 19 U.S. patent applications, four international PCT applications and 14 foreign patent applications. Of these, company-owned IP consists of 12 U.S. patent applications in nine patent families. PureTech exclusively licensed and co-own a patent portfolio of 10 patent families comprising 20 U.S. and foreign patent applications and four international PCT applications from Monash University. Of these patent applications, LYT-300 is covered by two patent families comprising one international PCT application and two U.S. patent applications, all of which are co-owned with Monash University. Any patents to issue from the in-licensed patent applications are expected to expire in 2035-2036 and any issued patents from the co-owned and company-owned patent applications are expected to expire in 2038-2041, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

Harnessing the natural lipid-trafficking pathways to transport drugs via the lymphatics