Harpoon Therapeutics Presents Data for New ProTriTAC™ Development Candidates in TROP2- and ITGB6-expressing Solid Tumors at AACR 2023
Harpoon Therapeutics has announced promising preclinical data for two new ProTriTAC™ T cell engager candidates targeting TROP2 and integrin-beta6 (ITGB6) in solid tumors. Presented at the AACR Annual Meeting, these candidates aim to improve therapeutic outcomes in cancers where these proteins are overexpressed. Notably, both candidates demonstrated effective anti-tumor activity in rodent models with complete tumor eradication observed at doses as low as 30 µg/kg. ITGB6 ProTriTAC exhibited favorable safety in cynomolgus monkeys, while TROP2 ProTriTAC showed some on-target toxicity at higher doses. The company aims to advance these findings to clinical studies, potentially enhancing treatment options for patients with solid tumors.
- Promising preclinical activity for ProTriTAC™ candidates targeting TROP2 and ITGB6 in solid tumors.
- Complete tumor eradication achieved at low doses (30 µg/kg) in rodent models.
- ITGB6 ProTriTAC demonstrated favorable safety and pharmacokinetics in cynomolgus monkeys.
- TROP2 ProTriTAC exhibited on-target toxicity at the highest tested dose (540 µg/kg).
Results support further investigation of two new ProTriTAC™ protease-activated T cell engager development candidates, with demonstrated therapeutic potential in a broad range of TROP2- and integrin-beta6 (ITGB6)-expressing solid tumors
SOUTH SAN FRANCISCO, Calif., April 17, 2023 (GLOBE NEWSWIRE) -- Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, today presented preclinical data on two new development candidates from the proprietary ProTriTAC™ platform in TROP2- and ITGB6-expressing solid tumors in poster presentations at the American Association for Cancer Research (AACR) Annual Meeting being held in Orlando, Fla., April 14-19, 2023. ProTriTAC is a T cell engager prodrug platform designed to remain inert systemically until its activation in the tumor by tumor-associated proteases and enable the safe targeting of broadly expressed solid tumor antigens. The first candidate, TROP2 ProTriTAC, is a protease-activated T cell engager prodrug targeting TROP2. The second candidate, ITGB6 ProTriTAC, is a protease-activated T cell engager prodrug targeting integrin-beta6.
“TROP2 and ITGB6 are tumor targets that are overexpressed in numerous solid tumor types and have demonstrated clinical utility when targeted as antibody drug conjugates,” said Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics. “However, significant unmet needs remain as both the depth and the durability of response with antibody drug conjugates are typically limited. The ability to safely target TROP2 and ITGB6 with T cell engagers, as the preclinical data with our ProTriTAC platform now demonstrate, warrants further study in the clinic.”
“Our ProTriTAC platform is designed to improve the therapeutic index of T cell engagers targeting solid tumor antigens,” said S. Jack Lin, Ph.D., Senior Director, Research and Preclinical Development, Harpoon Therapeutics. “The data presented at AACR further demonstrate that the ProTriTAC platform can be applied broadly to target different solid tumor antigens, which are often expressed elsewhere on normal tissues, and can achieve potent anti-tumor activities without incurring significant on-target off-tumor toxicities at the anticipated therapeutically relevant dose levels.”
Highlights from the posters include:
Abstract #2927: ITGB6 ProTriTAC™, a protease-activated T cell engager prodrug targeting Integrin-β6 for the treatment of solid tumors
ITGB6 protein is expressed in multiple tumor types, including cervical, lung, and head and neck, among others. In rodent established tumor models, ITGB6 ProTriTAC showed efficient prodrug activation and potent anti-tumor activity in vivo with complete tumor eradication at doses as low as 30 µg/kg. In cynomolgus monkeys, ITGB6 ProTriTAC showed favorable pharmacokinetic and safety profiles and was well-tolerated up to 540 µg/kg, the highest dose tested. Hematological changes consisted of minimally to moderately decreased neutrophils at all dose levels, as well as transient decreases in lymphocytes and basophils in week three of the study. There were no notable findings in plasma cytokines (IFNγ, IL-1β, IL-2, IL-6, IL-10, IL-8, TNF-α), coagulation, clinical chemistry, or urinalysis parameters. Additionally, there were no notable histopathological findings based on organ weight, gross and microscopic examination.
Abstract #2928: TROP2 ProTriTAC™, a protease-activated T cell engager prodrug targeting TROP2 for the treatment of solid tumors
TROP2 protein is expressed in multiple solid tumor types, including cervical, prostate and ovarian, among others. In rodent established tumor models, TROP2 ProTriTAC had highly potent anti-tumor activity in vivo with complete tumor eradication at doses as low as 30 µg/kg. In cynomolgus monkeys, TROP2 ProTriTAC showed favorable pharmacokinetics and was well-tolerated up to 180 µg/kg, whereas 540 µg/kg triggered on-target toxicity with mixed cell infiltrates in organs where normal tissue expression of TROP2 is expected. There were no notable findings in serum cytokines (IFNγ, IL-1β, IL-2, IL-6, IL-10, IL-8, TNF-α) throughout the study.
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.
Harpoon’s three distinct T cell engager platforms are designed to potentially allow more patients to get maximum clinical benefit while maintaining the best possible quality of life. Harpoon’s first platform, the constitutively active TriTAC® (Tri-specific T cell activating construct), is designed to minimize off-target toxicities, and is ideal for targets with limited on-target liabilities. The ProTriTAC platform offers similar advantages and adds an element of spatial control, 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™ platform (extended-release with slow activation in circulation) adds improved temporal control and is designed to be activated in the systemic circulation at a predefined rate to minimize on-target cytokine release syndrome (CRS).
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 www.harpoontx.com.
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 “may,” “expect,” “potential,” “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, 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.
Contacts:
Investors:
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Robert H. Uhl
Managing Director
858-356-5932
robert.uhl@westwicke.com
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FAQ
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