On April 16, 2018 Harpoon Therapeutics, a biotechnology company pioneering a new class of T cell engaging therapeutics based on its proprietary TriTAC platform, reported that preclinical data supporting the ongoing development of the platform and its two lead molecules, HPN424 and HPN536 (Press release, Harpoon Therapeutics, APR 16, 2018, View Source [SID1234525414]). These programs are the first of four programs using TriTAC technology, which has been designed for superior tumor penetration and efficacy in combating solid tumors. The company, which announced a series B financing and a partnership with AbbVie in 2017, anticipates filing investigational new drug (IND) applications and entering the clinic with these two compounds in the next 12 months. Data were presented at the 2018 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, held April 14-18, 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Harpoon created TriTAC as a best-in-class T cell engager platform optimized for the treatment of solid tumors," said Jerry McMahon, PhD, President and CEO, Harpoon Therapeutics. "The platform allows us to bring the success of T cell engagers targeting hematologic malignancies, like Blincyto, to solid tumor treatment. At Harpoon, we have optimized serum half-life, maximized tumor penetration, and engineered superior stability and manufacturability. These features have been the foundation for our discovery and development of a robust pipeline of drug candidates targeting PSMA, mesothelin, BCMA and DLL3."

Harpoon 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.

"We are excited to share these preclinical data for HPN424 and HPN536, which are designed to elicit targeted tumor cell destruction for both metastatic castration-resistant prostate cancer (mCRPC) and mesothelin-expressing tumors, respectively, such as lung, ovarian and pancreatic cancers," said Holger Wesche, PhD, Senior Vice President, Research. "We believe our new data underscore the significant impact our approach could make in advancing the field of immuno-oncology, and look forward to evaluating our compounds in clinical testing."

HPN424 Data Showed Potent T Cell Killing of Prostate Cancer Cells and Serum Half-Life Extension

HPN424 is a 50-kD single polypeptide containing three binding domains — for human PSMA, human serum albumin (HSA) 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 for a Phase 1 dose-escalation study in mCRPC patients planned to begin this year.

HPN536 Data Showed Potent Destruction of Mesothelin-Positive Cancer Cells and Evidence of Mechanism in a Primate Study

HPN536 is a 50-kD single polypeptide containing three binding domains — for human mesothelin (MSLN), HSA and human CD3. In preclinical studies, HPN536 demonstrated single-digit picomolar potency for MSLN-dependent T cell killing in a panel of human cancer cell lines derived from mesothelioma, pancreatic, non-small cell lung and ovarian tumors, and in vivo efficacy with efficacious doses in the low µg/kg range. An exploratory safety study in non-human primates showed that HPN536 was well tolerated and supported weekly dosing in humans. The compound was also shown to elicit T cell activation resulting in mesothelial hypertrophy and lymphocyte infiltration, which strongly supports tissue penetration, the mechanism of action of the TriTAC platform, and the planned Phase 1 study.

ABSTRACT INFORMATION

Abstract #1773
Title: "HPN424, a half-life extended, PSMA/CD3-specific TriTAC for the treatment of metastatic prostate cancer"
Date and Time: April 16, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 1

Abstract #1781
Title: "HPN536, a T cell-engaging, Mesothelin/CD3-specific TriTAC for the treatment of solid tumors"
Date and Time: April 16, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 1

Abstract #3814
Title: "TriTACs are novel T cell-engaging therapeutic proteins optimized for the treatment of solid tumors and for long serum half-life"
Date and Time: April 17, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 3