Phase I studies established proof-of-principle for the efficacy of oral sustained-release TGF?1 (TPX-6001) and ATRA (TPX-7001) nanoparticles in the treatment of IBD in a murine adoptive T-cell transfer model. Specifically, a two-week regimen of oral TPX-6001 and TPX-7001 achieved a 50-90 % reduction in the severity of multiple disease indicators in mice with advanced IBD. Importantly, co-administration of ATRA with TGF?1 was essential to achieving maximal therapeutic efficacy and disease amelioration was associated with enhanced T-regulatory cell activity in the colon. Phase II work is designed to further optimize therapy protocol in the pre-clinical murine IBD model, establish scale-up manufacturing process and complete toxicology studies leading up to IND filing.
In Aim 1, pre-clinical optimization work is completed. To this end, combination TGF?1 and ATRA dosages are optimized first. This combination is then used to identify the optimal therapeutic regimen, determine the ability of treatment to maintain disease remission in the long-term and monitor side-effects.
In Aim 2, scale-up process parameters are established to achieve bulk drug production. Batch-to-batch uniformity and shelf-life are determined for the scaled-up product.
Aim 3 studies are designed to complete toxicokinetics in 2 mammalian species. These studies are performed in collaboration with the Navigators Toxicology Group at Charles River Laboratories. The data obtained in Aims 1-3 are then utilized in the preparation of an Investigational New Drug (IND) application to the FDA (Aim 4). Successful completion of Phase II studies will facilitate the advancement of TPX-6001/7001 to a Phase I clinical trial in IBD patients.

Public Health Relevance

Current therapies for inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis fail a considerable percentage of patients due to ineffectiveness or therapy limiting side effects. TherapyX, Inc. is developing a more advanced drug delivery system that targets Transforming Growth Factor ?-1 and Retinoic Acid to the site of inflammation in the gut thereby reducing systemic side effects. This therapy has the potential to significantly improve morbidity and quality of life of those suffering with IBD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI080009-04
Application #
8441611
Study Section
Special Emphasis Panel (ZRG1-DKUS-E (10))
Program Officer
Prograis, Lawrence J
Project Start
2008-07-20
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2015-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$999,998
Indirect Cost
Name
Therapyx, Inc.
Department
Type
DUNS #
145056607
City
Buffalo
State
NY
Country
United States
Zip Code
14214