Harpoon Therapeutics Presents Data on its TriTAC-XR Platform

Harpoon Therapeutics, Inc. recently presented 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) in Washington, DC.

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, PhD, 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,” added 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.

Harpoon Therapeutics is a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct (TriTAC) platform, Harpoon is developing a pipeline of novel TriTACs initially focused on the treatment of solid tumors and hematologic malignancies. HPN424 targets PSMA and is in a Phase 1/2a trial for metastatic castration-resistant prostate cancer. HPN536 targets mesothelin and is in a Phase 1/2a trial for cancers expressing mesothelin, initially focused on ovarian and pancreatic cancers. HPN217 targets BCMA and is in a Phase 1/2 trial for relapsed, refractory multiple myeloma. HPN328 targets DLL3 and is in a Phase 1/2 trial for small cell lung cancer and other DLL3-associated tumors. Harpoon has also developed a proprietary ProTriTAC platform, which applies a prodrug concept to its TriTAC platform to create a therapeutic T cell engager that remains inactive until it reaches the tumor. The company’s third proprietary technology platform, extended release TriTAC-XR, is designed to mitigate cytokine release syndrome. For more information, visit www.harpoontx.com.