Harpoon Therapeutics treats first patient with HPN424 in phase I clinical trial of metastatic castration-resistant prostate cancer (mCRPC) patients.
HPN424, First-in-Class TriTAC™ T Cell Redirection Therapy, Targets Prostate-Specific Membrane Antigen (PSMA)
Clinical Data Expected in 2019
South San Francisco – August 6, 2018 – (BUSINESS WIRE) – Harpoon Therapeutics, an immuno-oncology company pioneering a new class of T cell engaging therapeutics, announced today 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.
The Phase 1 trial is a multicenter, multinational, open-label, ascending dose study designed to evaluate the safety, tolerability and pharmacokinetics of HPN424 in approximately 40 patients with metastatic prostate cancer. 
“We are pleased to initiate Harpoon’s first clinical trial with HPN424 in patients with advanced prostate cancer, an important milestone that marks our transition to a clinical-stage company,” said Jerry McMahon, PhD, President and Chief Executive Officer of Harpoon Therapeutics. “HPN424 is the first TriTAC compound to enter clinical testing and represents a novel class of T cell therapeutics aiming to achieve superior efficacy in penetrating and killing solid tumors. Data is expected in 2019, and should provide the safety assessment, pharmacokinetics and pharmacodynamics to determine the optimal dose and regimen for our additional planned trials in prostate cancer, the third leading cause of cancer deaths for men in the U.S.”
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. For more information about the trial, please visit clinicaltrials.gov, identifier number NCT03577028.
“Immunology represents a new frontier for the treatment of prostate cancer,” said Charles G. Drake, MD, PhD, Director of Genitourinary Oncology at New York Presbyterian/Columbia University Cancer Center, Co-director of Columbia’s Cancer Immunotherapy Program and Scientific Advisory Board member at Harpoon. “Each year in the U.S., approximately 26,000 men die from prostate cancer following treatment with current available therapies. HPN424, an innovative biologic designed to activate T cells in the tumor, is highly potent in killing prostate cancer cells in preclinical models and could be a promising option for these men with advanced disease.”
“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 about 80 hours supporting once-weekly administration.  Link to HPN424 AACR 2018 Poster
Harpoon Therapeutics is a clinical-stage immuno-oncology company founded by Patrick Baeuerle, PhD, a pioneer in the development of T cell engaging therapies, and MPM Capital. The company is focused on the discovery and development of novel T cell engaging biologics for the treatment of cancer. Harpoon Therapeutics created a novel T cell redirection platform called TriTAC (Tri-specific T cell Activating Construct) to unleash the targeted cell-killing properties of a patient’s own immune system through T cell activation. This approach has been optimized to overcome the limitations of existing immunotherapies to penetrate tissues and extend serum exposure for superior efficacy in solid tumors. Harpoon is developing a robust pipeline of TriTAC candidates. Harpoon has initiated a Phase 1 clinical trial for lead candidate HPN424, a prostate-specific membrane antigen (PSMA)-targeting TriTAC, and expects to file an investigational new drug application for HPN536, a mesothelin-targeting TriTAC soon. For more information, please visitwww.harpoontx.com.
Harpoon Therapeutics
Susan Kinkead
Kinkead Communications, Inc.