PureTech Health plc, a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, announced the publication of preclinical proof-of-concept demonstrating that PureTech’s Glyph platform can enhance the oral bioavailability of buprenorphine (BUP), a clinically-validated opioid replacement therapy, further expanding the range of clinically-validated drug classes shown to be amenable to the Glyph technology. The paper, published in Frontiers in Pharmacology1, applies the Glyph technology to BUP, a potent analgesic that is widely used for severe pain management and opioid replacement therapy but is not currently available in an ingestible oral dosage form due to poor oral bioavailability. In preclinical models, the researchers observed increases in bioavailability of up to 20-fold and statistically significant increases in lymphatic transport.
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“The therapeutic potential of buprenorphine is potentially limited by a lack of systemic exposure after the administration of a capsule formulation that can be swallowed. The ability to develop an oral buprenorphine product with high bioavailability could potentially address a range of important unmet clinical needs and offer more convenience for patients,” said Christopher Porter, Ph.D., Director of the Monash Institute of Pharmaceutical Sciences at Monash University in Melbourne, lead author of the study and PureTech collaborator. “Results from this study further amplify the breadth of the Glyph delivery technology and its ability to use new chemistry and molecules for versatile applications.”
The Glyph technology generates novel orally dosed prodrugs by reversibly linking small molecule drugs to dietary fat molecules. This linkage is designed to channel the drugs directly into the systemic circulation via the lymphatic system, thereby bypassing first-pass liver metabolism which typically degrades many drugs and reduces their systemic exposure. The Glyph technology is being developed to be applicable to a range of clinically validated drugs with poor bioavailability, including neuromodulators such as allopregnanolone (with the clinical-stage therapeutic candidate, LYT-300) or immune modulators that could directly target the mesenteric lymph nodes.
“The research serves as another proof-of-concept for our Glyph platform and how this innovative drug delivery technology can be applied to a range of diseases,” said Joseph Bolen, Ph.D., Chief Scientific Officer of PureTech. “This latest research reinforces our commitment to leveraging validated biology to accelerate the development of the Glyph portfolio to improve the oral bioavailability and/or lymphatic targeting of proven drugs.”
PureTech’s LYT-300 is the first therapeutic candidate generated by the Glyph technology platform to enter the clinic. LYT-300 is an oral formulation of the clinically validated neurosteroid allopregnanolone, in development for the potential treatment of a range of neurological and neuropsychological conditions. An injectable formulation of allopregnanolone is approved by the United States Food and Drug Administration (FDA) for the treatment of postpartum depression as a 60-hour infusion, a method of administration that has inherent limitations. Synthetic oral analogs of allopregnanolone have had variable clinical success, and their comparable activity with natural allopregnanolone remains to be established.