Harpoon Therapeutics Begins Trial of Novel Immuno-Oncololgy Drug in Patients with Metastatic Castration-Resistant Prostate Cancer

August 6, 2018
  • Clinical data expected in 2019
  • HPN424 is designed as an ‘off-the-shelf’ T cell therapy
  • HPN424 serum half-life of 80 hours supporting once-weekly administration

Harpoon Therapeutics announced on 8/6/18 that the first patient has been treated with HPN424 in a Phase 1 clinical study of metastatic castration-resistant prostate cancer (mCRPC) patients. HPN424 is the first of multiple compounds in development that are based on the company’s TriTAC™ (Tri-specific T cell Activating Construct) platform and designed to penetrate solid tumors, have extended serum half-life, and recruit patients’ own T cells to destroy malignant tumor cells.

Harpoon has previously presented preclinical data which highlighted the novel aspects of its proprietary TriTAC platform to potentially overcome the limitations of existing bispecific antibody-based and CAR-T therapies. The TriTAC platform uses a single flexible polypeptide comprised of three binding domains, and is designed to be the smallest, half-life extended T cell engaging format without the potential liabilities associated with conventional bispecific antibodies.

“HPN424 is designed as an ‘off-the-shelf’ T cell therapy which can overcome loss of human leukocyte antigen (HLA) expression – a frequent mechanism by which cancer cells escape T cell recognition,” said Che-Leung Law, PhD, Vice President of Translational Medicine. “Pharmacological insights gleaned from the study should help inform development of both HPN424 and our pipeline of additional products - targeting mesothelin (MSLN), B-cell maturation antigen (BCMA) and DLL3 - in the near future.”

HPN424 is a 50-kD single polypeptide that contains three binding domains — for human PSMA, human serum albumin and human CD3. In preclinical studies, HPN424 demonstrated single-digit picomolar potency for PSMA-dependent T cell killing in a panel of human prostate cancer cell lines, which translated to in vivo efficacy with efficacious doses in the low µg/kg range. HPN424 was well tolerated in a multi-dose safety study in non-human primates and showed a serum half-life of 80 hours supporting once-weekly administration.

In the first phase of the study, HPN424 will be administered once weekly to patients via intravenous (IV) infusion with dose escalation until a therapeutic dose level has been reached. Following dose escalation, Harpoon will further evaluate the safety and efficacy of HPN424 in additional cohorts of patients at the recommended Phase 2 dose established in the first phase of the study.

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