Harpoon Therapeutics Presents Preclinical Results for Novel T Cell Engagers HPN217 and HPN328 at AACR 2023
- Preclinical results for HPN328 suggest potential for long-term anti-tumor immunity and durable responses in patients, as well as utility of combining anti-PD-L1 antibodies to enhance anti-tumor activity
- γ-secretase inhibitors increased the potency of HPN217 in vitro in multiple cell lines, supporting further study of combination approach
“These data provide further validation of our proprietary TriTAC T cell engager platform, indicating potential for long-term immunity induced by HPN328, as well as clinical effect in combination with anti-PD-L1 antibodies,” said
“With our Phase 1 trial ongoing and further studies planned, we look forward to continuing our clinical development efforts for these two promising programs,” added
Highlights from the posters include:
Abstract #4131: Long-term anti-tumor immunity induced by HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, in a preclinical immunocompetent mouse model
In an immunocompetent MC38-hDLL3 murine cancer model, HPN328 showed dose dependent anti-tumor activity and increased CD8+ tumor infiltrated lymphocyte (TIL) activation which was maintained upon reintroduction of a second tumor on the opposite flank, and discontinuing treatment. These results suggested that HPN328 can induce epitope spreading and prolonged anti-tumor immunity, with an increase in memory T cells, suggesting a novel mechanism for its activity and efficacy in vivo. Overall, these findings indicate that long-term anti-tumor immunity induced by HPN328 can potentially lead to more durable anti-tumor responses in cancer patients.
Abstract #5070: Anti-tumor activity of HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, is enhanced by combining with an anti-PD-L1 antibody in an immunocompetent mouse model
In an immunocompetent mouse model, sub-therapeutic doses of HPN328 in combination with an anti-PD-L1 antibody demonstrated enhanced, dose dependent anti-tumor activity when compared to either treatment alone and showed increased activation in memory CD8+ T cells. These results demonstrate the utility of combining anti-PD-L1 antibodies to enhance the anti-tumor activity of HPN328 and further supports investigation of this combination approach in patients. Clinical studies of HPN328 in combination with atezolizumab are planned.
Abstract #5081: Anti-tumor activity of HPN217, a BCMA-targeting tri-specific T cell engager, is enhanced by γ-secretase inhibitors in preclinical models
γ-secretase inhibitors (GSIs) have been shown to increase membrane bound BCMA expression on multiple myeloma cells, providing a rationale for studying this combination approach. In preclinical mouse models, γ-secretase inhibitors increased the potency of HPN217 in vitro in multiple cell lines. Specifically, combination therapy with 1mg/kg LY-3039478 and a subtherapeutic dose of 4ug/kg HPN217 led to decreased tumor burden and increased survival in a disseminated MOLP8 xenograft compared to either monotherapy alone.
For more details about the AACR Annual Meeting, please visit: https://www.aacr.org/meeting/aacr-annual-meeting-2023/
The posters will be available on Harpoon’s website following today’s presentations.
HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC®) platform designed to recruit a patient’s own immune cells to kill tumor cells. HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments.
HPN328 targets delta-like canonical Notch ligand 3 (DLL3) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC®) platform designed to recruit a patient’s own immune cells to kill tumor cells. HPN328 is being evaluated as monotherapy in an ongoing open-label, multicenter two-part study to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3.
Harpoon Therapeutics is a clinical-stage immuno-oncology 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. 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. Harpoon’s third proprietary technology platform, extended release TriTAC-XR, is designed to mitigate cytokine release syndrome. For additional information about
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