Harpoon drug sunk by modest activity, challenging tolerability, forcing pivot from prostate cancer prospect

Harpoon Therapeutics has given up on its onetime lead prospect HPN424. A phase 1/2a prostate cancer clinical trial found the PSMA-targeting T-cell engager had “modest activity with a tolerability profile that has been challenging,” driving Harpoon to discontinue development and focus on other assets.

HPN424 spearheaded Harpoon’s move into the clinic, delivering preliminary phase 1 early in 2019 the biotech used as the centerpiece of an IPO filing that generated $76 million shortly thereafter. At that time, Harpoon pitched HPN424 as a showcase of the potential of its TriTAC T-cell engager approach to improve on existing bispecifics.

Other candidates now carry the burden of showing the value of the TriTAC approach. In a statement, Harpoon CEO Julie Eastland said management decided to discontinue clinical development of HPN424 after reviewing data on the candidate. 

Eastland’s predecessor, Jerry McMahon, had a different view when Harpoon presented clinical data last summer, arguing the study showed “clinical activity, target engagement and a manageable safety” in a heavily pretreated patient population. At that time, Harpoon pointed to a confirmed partial response in a study of 89 patients as evidence of the anti-tumor activity of HPN424.

Harpoon went into 2022 aiming to complete dose escalation in the second half of the year. The new plan is to wind the clinical trial down across the remainder of the year while ensuring patients can access HPN424 for their course of therapy.

The discontinuation confirms a pivot Harpoon has hinted at in its recent updates, which have listed drug candidates including HPN328 and HPN217 above HPN424 in the pipeline pecking order. Harpoon expects to determine the phase 2 doses of HPN328, a drug intended for use in tumors associated with DLL3 expression, and BCMA prospect HPN217 this year.