Harpoon raises $70M to trial solid tumor T-cell engagers

Harpoon Therapeutics has raised $70 million to advance its pipeline of T-cell engagers. The series C sets Harpoon up to move candidates targeting mesothelin and BCMA into human testing next year.

South San Francisco-based Harpoon set up shop to create T-cell engagers capable of treating solid tumors. Amgen validated the concept of using a drug to redirect T cells to attack tumors when it won approval for Blincyto in 2014. But while Blincyto showed that T-cell engagers can treat blood cancers, the role of the format in solid tumors remains uncertain. Tissue penetration is one of several barriers to the use of T-cell engagers in solid tumors. Harpoon thinks its TriTAC format can clear these barriers.

Boosted by $70 million in series C funds, AbbVie-partnered Harpoon is set to put that idea to the test. The funding will enable Harpoon to continue testing its lead drug, the PSMA-targeting TriTAC HPN424, in a phase 1 metastatic castration-resistant prostate cancer trial. And add the mesothelin- and BCMA-targeting TriTACs HPN536 and HPN217 to its roster of clinical-phase candidates next year.

HPN536 is being developed as a treatment for cancers that express mesothelin, an antigen that is found in malignant mesothelioma and pancreatic, ovarian and lung tumors. HPN217 is advancing in parallel as a treatment for multiple myeloma.

All the assets are derived from Harpoon’s TriTAC platform. TriTACs are single polypeptides, around one-third the size of monoclonal antibodies, that have three binding domains. As in a bispecific T-cell engager, one TriTAC domain binds to a cancer surface antigen and another engages T cells. The third, TriTAC-specific domain binds albumin to extend the serum half-life.

On paper, the small size of TriTACs should enable them to penetrate solid tumors, opening up a new set of indications to treat with T-cell engagers. And the addition of a third, albumin-binding domain will significantly improve the half-life over bispecific antibodies.

Blincyto has a half-life of around two hours, meaning it must be administered via continuous intravenous infusion. In contrast, preclinical tests suggest TriTACs have a half-life of three to four days. Harpoon thinks the pharmacokinetics of HPN424 will permit once- or twice-weekly dosing.

Harpoon has persuaded investors to buy into the potential of the TriTAC format. OrbiMed came on board as lead new investor in the series C. Fellow new investors Cormorant, Ridgeback Capital Investments, Lilly Asia Ventures and NS Investment contributed, too, as did existing backers MPM Capital, Oncology Impact Fund, Arix Bioscience, New Leaf Venture Partners and Taiho Ventures.

The syndicate’s cash will support the advance of three TriTACs into and through the clinic, and leave enough leftover for Harpoon to advance drugs derived from its second platform, ProTriTAC. Assets derived from the platform have many of the features of TriTACs. The twist is that ProTriTACs remain inactive until they meet tumor-associated proteases, potentially cutting damage to healthy tissues.

Harpoon plans to move a ProTriTAC candidate into IND-enabling studies next year.