On April 18, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported preclinical data for two of its key clinical programs, HPN328 and HPN217, in three poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held in Orlando, Fla., April 14-19, 2023 (Press release, Harpoon Therapeutics, APR 18, 2023, View Source [SID1234630266]). 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. HPN328 is Harpoon’s half-life extended TriTAC that targets delta-like canonical Notch ligand 3 (DLL3).
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"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 Banmeet Anand, Ph.D., Senior Vice President, Translational Medicine, Harpoon Therapeutics. "Results also support our continued clinical development efforts for HPN217, with encouraging preclinical results in combination with γ-secretase inhibitors (GSIs)."
"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 Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics.
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 (Free AACR Whitepaper) Annual Meeting, please visit: View Source
The posters will be available on Harpoon’s website following today’s presentations.
About HPN217
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.
In November 2019, Harpoon Therapeutics and AbbVie announced a licensing agreement and option to advance HPN217 and expand an existing discovery collaboration. Under the terms of the agreement, AbbVie may exercise its option to license HPN217 after completion of the Phase 1 clinical trial.
In March 2022, the FDA granted Fast Track designation to HPN217, underscoring its potential to address a serious unmet medical need for patients with relapsed, refractory multiple myeloma.
About HPN328
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.
In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to HPN328 for the treatment of small cell lung cancer (SCLC).