Harpoon Therapeutics Announces Data from Poster Presentations at the AACR Annual Meeting 2021
Key findings of each of the posters are described below.
FLT3-targeting TriTACs® are T cell engagers for treatment of acute myeloid leukemia
FLT3 RNA is found in over 95% of AML samples and FLT3 mutations are oncogenic and found in approximately 30% of AML. This provides the rationale that a FLT3-targeting T cell engager could be a valid therapeutic approach for AML. Data show that FLT3 TriTACs® bind human and non-human primate FLT3, and can redirect T cells to kill FLT3 expressing cells in vitro. In addition, FLT3 TriTACs® eliminate FLT3 expressing cells in a non-human primate study and are well tolerated after a single dose.
ProTriTAC™ is a modular and robust T cell engager prodrug platform with therapeutic index expansion observed across multiple tumor targets
ProTriTAC™ is a conditionally active T cell engager platform that is designed to be preferentially active in the tumor. This enables the targeting of more broadly expressed solid tumor targets and allows T cell engagers to address more tumor types. Data presented today illustrate the consistency and the robustness of the ProTriTAC™ platform in vitro and in vivo as demonstrated by cell-based assays, pharmacokinetic studies in non-human primates, and therapeutic index assessments in tumor-bearing animals across multiple tumor targets. IND-enabling studies are currently underway for Harpoon’s first ProTriTAC™ program (HPN601).
Combinatorial antitumor effects of CD3-based trispecific T cell activating constructs (TriTACs®) and checkpoint inhibitors in preclinical models
TriTAC® molecules induce PD1/PD-L1 expression on T cells which may lead to suppression of the cytolytic functions of TriTAC® activated T cells. PD1 can be readily detected on T cells subsequent to the engagement of the TCR by the TriTAC® molecule. Data presented today show that the combination of HPN536 with a PD-L1 inhibitor led to more potent antitumor activity in an MSLN expressing ovarian cancer xenograft model. Similar enhanced anti-tumor effects were shown in an MSLN expressing lung cancer model for HPN536 in combination with anti-PD1 or an anti-PD1 antibody. These data demonstrate the potential utility of PD1/PD-L1 blockade to enhance the potency of TriTAC® mediated tumor cell killing.
“These data from Harpoon’s poster presentations at AACR underscore the potential for further investigations of additional tumor targets, combination approaches with TriTACs®, and conditionally active T cell engager prodrugs, or ProTriTACs™, which may lead to greater tumor specificity, enhanced efficacy, and improved tolerability for patients,” said
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Source: Harpoon Therapeutics