Harpoon Therapeutics Presents Data on its TriTAC-XR Platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer
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
“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
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 additional information about
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This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “could,” “expect,” “intend,” “potential,” “suggest,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Harpoon Therapeutics’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon Therapeutics’ clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the development and advancement of Harpoon Therapeutics’ platforms and product candidates, ability of TriTAC-XR T cell engager platform to mitigate toxicities, such as cytokine release syndrome, and improve the safety of T cell engagers, and to enable the use of T cell engagers for the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies, and other statements that are not historical fact. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, preliminary data and trends may not be predictive of future data or results, may not demonstrate safety or efficacy or lead to regulatory approval by the FDA or other regulatory agencies, clinical trial site activation or enrollment rates that are lower than expected, unanticipated or greater than anticipated impacts or delays due to COVID-19, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the timing and results of unexpected litigation or other disputes, and the sufficiency of Harpoon Therapeutics’ cash resources. These and other factors that may cause Harpoon Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Harpoon Therapeutics’ filings with the U.S. Securities and Exchange Commission, including under “Risk Factors” in Harpoon Therapeutics’ quarterly report on Form 10-Q for the quarter ended September 30, 2021 and future filings by Harpoon Therapeutics. Except as required by law, Harpoon Therapeutics assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
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Source: Harpoon Therapeutics