Reference number : GC-2017-Q4-00435, amendment number : , agreement type : G, recipient legal name : De Crescenzo, Gregory (École Polytechnique de Montréal), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Engage Grants for universities, program name french : Subventions d'engagement partenarial pour les universités, program purpose english : Transforming growth factor beta (TGF-ß) is a pleiotropic cytokine with essential roles in normal embryonic_x000D_
development and tissue homeostasis. The role of excessive TGF-ß action in fibrosis is well documented._x000D_
Therefore, it is of interest to develop drugs that block TGF-ß signaling for therapeutic benefit. This therapeutic_x000D_
niche is now being explored by Formation Biologics, a Canadian company focusing on the development of_x000D_
TGF-ß inhibitors. Formation has a successful drug development record with one product in phase I clinical_x000D_
trials, and a second in IND-enabling development. To continue its efforts in the development of specific TGF-ß_x000D_
inhibitors (i.e. specific to each isoform within the TGF-ß superfamily), Formation Biologics is now interested_x000D_
in exploring promising alternatives to antibody-based therapeutics. The proposed research thus focuses on_x000D_
harnessing the TGF-ß-neutralizing potential of TGF-ß receptor extracellular domains to develop potent TGF-ß_x000D_
antagonists. More specifically, the proposal is to physically combine various receptor extracellular domains to_x000D_
improve their TGF-ß binding and sequestration efficiency while taking advantage of their binding specificity. If_x000D_
performed with a classical experimental approach (i.e., the design of chimeric proteins corresponding to the_x000D_
fusion of two distinct receptors, their purification and related assays), such a study would be extremely_x000D_
time-consuming if one considers the number of TGF-ß isoforms, the number of receptors they bind to, as well_x000D_
as the number of resulting receptor combinations. Using a unique molecular adaptor strategy emanating from_x000D_
previous work performed in De Crescenzo's lab, the inhibition of TGF-ß signaling by different TGF-ß receptor_x000D_
combinations will be tested more rapidly by setting an innovative mix-and-match strategy. The expected_x000D_
outcome is a competitive and novel strategy to inhibit TGF-ß signaling. Successful completion of this project_x000D_
will provide Formation Biologics with a new therapeutic avenue to inhibit TGF-ß signaling, hence promoting_x000D_
the development of new drugs, and thus directly benefiting the Canadian patient population and economy., program purpose french : Transforming growth factor beta (TGF-ß) is a pleiotropic cytokine with essential roles in normal embryonic_x000D_
development and tissue homeostasis. The role of excessive TGF-ß action in fibrosis is well documented._x000D_
Therefore, it is of interest to develop drugs that block TGF-ß signaling for therapeutic benefit. This therapeutic_x000D_
niche is now being explored by Formation Biologics, a Canadian company focusing on the development of_x000D_
TGF-ß inhibitors. Formation has a successful drug development record with one product in phase I clinical_x000D_
trials, and a second in IND-enabling development. To continue its efforts in the development of specific TGF-ß_x000D_
inhibitors (i.e. specific to each isoform within the TGF-ß superfamily), Formation Biologics is now interested_x000D_
in exploring promising alternatives to antibody-based therapeutics. The proposed research thus focuses on_x000D_
harnessing the TGF-ß-neutralizing potential of TGF-ß receptor extracellular domains to develop potent TGF-ß_x000D_
antagonists. More specifically, the proposal is to physically combine various receptor extracellular domains to_x000D_
improve their TGF-ß binding and sequestration efficiency while taking advantage of their binding specificity. If_x000D_
performed with a classical experimental approach (i.e., the design of chimeric proteins corresponding to the_x000D_
fusion of two distinct receptors, their purification and related assays), such a study would be extremely_x000D_
time-consuming if one considers the number of TGF-ß isoforms, the number of receptors they bind to, as well_x000D_
as the number of resulting receptor combinations. Using a unique molecular adaptor strategy emanating from_x000D_
previous work performed in De Crescenzo's lab, the inhibition of TGF-ß signaling by different TGF-ß receptor_x000D_
combinations will be tested more rapidly by setting an innovative mix-and-match strategy. The expected_x000D_
outcome is a competitive and novel strategy to inhibit TGF-ß signaling. Successful completion of this project_x000D_
will provide Formation Biologics with a new therapeutic avenue to inhibit TGF-ß signaling, hence promoting_x000D_
the development of new drugs, and thus directly benefiting the Canadian patient population and economy., agreement title english : Next-generation of Transforming Growth Factor ß inhibitors, agreement title french : Next-generation of Transforming Growth Factor ß inhibitors, agreement number : EGP, agreement value : 25000.0, agreement start date : 2018-03-07, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2018-2019)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada