On April 10, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing a novel class of T cell engagers, reported the availability of three poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Harpoon Therapeutics, APR 10, 2021, View Source [SID1234577851]). The presentations will be available beginning today at 8:30 a.m. ET through the virtual meeting website at www.aacr.org and on the Harpoon corporate website at www.harpoontx.com.
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Key findings of each of the posters are described below.
FLT3-targeting TriTACs are T cell engagers for treatment of acute myeloid leukemia
Presenter: Richard J. Austin, Ph.D., Abstract #: 2643
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
Presenter: S. Jack Lin, Ph.D., Abstract #: 933
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
Presenter: Mary Ellen Molloy, Ph.D. Abstract #: 1573
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 (Free AACR Whitepaper) 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 Holger Wesche, Ph.D., chief scientific officer of Harpoon Therapeutics. "I am encouraged by these findings and look forward to future validation in the clinic."