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

SOUTH SAN FRANCISCO, Calif., April 18, 2023 (GLOBE NEWSWIRE) -- Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, today presented preclinical data for two of its key clinical programs, HPN328 and HPN217, in three poster presentations at the American Association for Cancer Research (AACR) Annual Meeting being held in Orlando, Fla., April 14-19, 2023. 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).

“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 Annual Meeting, please visit: 

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).

About Harpoon Therapeutics

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 Harpoon Therapeutics, please visit .

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “look forward,” “may,” “suggest,” “plan,” “potential,” “continued,” “further,” “will,” 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 expected progress, results, and plans pertaining to Harpoon Therapeutics’ clinical trials, the association of interim clinical data and preclinical results with potential treatment outcomes, the possibility and timing of AbbVie’s option to license HPN217 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, 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’ annual report on Form 10-K for the year ended December 31, 2022, 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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