LYT-300

 

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LYT-300
Oral Allopregnanolone
Neurological indications

Preclinical

Neurological indications


LYT-300 is an oral form of FDA-approved allopregnanolone, which is currently marketed in the U.S. as ZulressoTM and administrated as a 60-hour intravenous infusion. An oral form of allopregnanolone and other neurosteroids would enable the development of these natural molecules for treating a range of neurological and neuropsychological conditions.
Phase completedPhase in progress
Targeting neurological and neuropsychological conditions by trafficking therapeutics via the lymphatic system

LYT-300, which is an oral form of FDA-approved allopregnanolone, a natural neurosteroid, is in development to potentially address a range of neurological and neuropsychological conditions. It is the most advanced product candidate from the GlyphTM technology platform, which harnesses the role of the lymphatic system in the absorption of dietary lipids to orally administer and traffic therapeutics via the lymphatic system.

  • Program Discovery Process by the PureTech Team
    • PureTech sought out different approaches to harness the role of the lymphatic system in the absorption of dietary lipids to orally administer and traffic therapeutics via the lymphatic system. This led to the development of LYT-300, a preclinical product candidate developed using PureTech’s Glyph technology platform, targeting neurological and neuropsychological conditions.
  • Innovative Approach to Solving the Problem
    • PureTech is developing a synthetic lymphatic-targeting chemistry platform called Glyph, which employs the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system by targeting the mesenteric lymph nodes and bypassing first-pass metabolism. 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. 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. This drug is administered via a 60 hour IV infusion, leading to sustained unmet need for novel therapies.
    • Allopregnanolone, and neurosteroids in general as a class of potent endogenous natural small molecules, have been recognized over the past three decades for their therapeutic potential to treat a range of neurological and neuropsychological conditions such as epileptic disorders, fragile X syndrome, fragile X tremor-associated syndrome, anxiety, depression, essential tremor, and sleep disorders, among others. The major hurdles associated with the translation of these compounds have been:
      • The inability to create an oral formulation due to first pass metabolism by the liver; and
      • The inability to administer them chronically to patients – essential for treating central nervous system (CNS) disorders.
    • An oral form of allopregnanolone and other neurosteroids would enable the development of these natural molecules for treating a range of neurological and neuropsychological conditions.
  • 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.
  • Milestones Achieved
    • PureTech created a library of lipid prodrugs of allopregnanolone and showed that orally dosing these prodrugs achieved therapeutically relevant plasma levels in small and large animal models. These studies, coupled with other preclinical studies, support the possible utility of this approach for converting natural allopregnanolone into an orally-dosed drug as well as for numerous other potential therapeutics with intrinsic hepatic metabolism liabilities and oral absorption limitations. 
    • PureTech measured plasma levels of allopregnanolone after oral administration of lymphatic targeting prodrug of allopregnanolone or unmodified allopregnanolone in preclinical models of dogs and non-human primates. Apparent bioavailability of free allopregnanolone versus intravenous, or IV, was calculated to be over 30 percent in both species.
  • Expected Milestones
    • PureTech expects to initiate a first-in-human clinical trial with LYT-300 by the end of 2021.

Oral allopregnanolone for a range of neurological disorders