On November 12, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported a poster with preclinical data on its TriTAC-XR T cell engager platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Washington, D.C (Press release, Harpoon Therapeutics, NOV 12, 2021, View Source [SID1234595443]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The poster, titled "TriTAC-XR is an extended-release T cell engager platform designed to minimize cytokine release syndrome (CRS) by reducing Cmax in systemic circulation," showcased preclinical data supporting the novel platform. The platform is designed to minimize on-target cytokine release syndrome, a hallmark of many T cell engagers that can lead to dose limiting toxicities.
Studies in non-human primates with FLT3-targeting T cell engagers confirmed that the slow build-up of active drug and the reduction of differences in peak-to-trough drug concentrations can reduce CRS and improve the safety of T cell engagers. Importantly, the reduction of cytokine release could be achieved while maintaining efficacy in in vivo models. When compared to a TriTAC with the same three binding domains, the TriTAC-XR was able to deplete FLT3-expressing cells with comparable potency despite a 100x reduction in cytokines in cynomolgus monkeys.
"These encouraging data demonstrate that our TriTAC-XR T cell engager platform has the potential to meaningfully mitigate CRS, and we intend to explore if this approach enables the use of T cell engagers for the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies," said Holger Wesche, Ph.D., Chief Scientific Officer of Harpoon Therapeutics.
"The introduction of TriTAC-XR represents the third T cell engager platform and the second protease-activated T cell engager prodrug platform from Harpoon. This further showcases the productivity and creativity of our research efforts, and our commitment to the development of best-in-class T cell engagers," said Julie Eastland, Chief Executive Officer of Harpoon Therapeutics.
Harpoon’s first platform, the constitutively active TriTAC, is designed to minimize off-target toxicities, and is ideal for targets with limited on-target liabilities. The ProTriTAC platform offers similar advantages with activation directed primarily to the tumor microenvironment. This spatial control of activation may address on-target tissue damage, hence enabling an expansion of the T cell engager target space. The TriTAC-XR now adds improved temporal control and is designed to be activated in the systemic circulation at a predefined rate to minimize on-target CRS.
Preclinical data from the TriTAC platform demonstrated:
TriTAC-XR is an extended-release T cell engager platform designed to mitigate cytokine release syndrome by releasing active T cell engagers from an inactive prodrug in a temporally controlled fashion, thus avoiding the very high exposures (Cmax) that occur shortly after administration with constitutively active molecules.
A single dose of FLT3 TriTAC-XR produced similar PD effects with significantly lower cytokines than a comparable TriTAC in non-human primate animal models.
The expected safety improvement of TriTAC-XR could enable the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies.