Harpoon Therapeutics Inc. and Abbvie Inc. have cut their second deal in little more than two years as they embark upon an exclusive worldwide option and license transaction for HPN-217, Harpoon’s B-cell maturation antigen T-cell engagers targeting solid tumors and hematologic malignancies.

This expands their existing collaboration for up to six additional targets. In October 2017, the two entered an immuno-oncology research alliance incorporating Harpoon’s platform with Abbvie’s research-stage immuno-oncology targets to develop cancer therapeutics.

“We already had a relationship with them from that transaction,” Gerard McMahon, Harpoon’s president and CEO, told BioWorld. “So when we went looking for a commercial partner in multiple myeloma, recognizing it’s a focused disease with significant competition, we approached them if they were interested in expanding research collaboration.”

In the October 2017 agreement, South San Francisco-based Harpoon granted Abbvie an option to license worldwide exclusive rights to HPN-217 through its phase I/II trials. Should it exercise the option, Abbvie would conduct all the clinical development, manufacturing and commercialization duties. It could also exercise its option to license HPN-217 after completing the phase I/II study. The agreement comes with a transaction value of $510 million up front, with option and milestone payments and global sales royalties.

Gerard McMahon, president and CEO, Harpoon

In the new and expanded deal, Abbvie receives worldwide exclusive rights to develop and commercialize two new molecules from Harpoon’s Tri-specific T cell Activating Construct (Tritac) platform that are engineered for two selected targets. It has the option to choose up to four additional targets. For each selected target, Harpoon could receive up to $310 million in up-front and potential development, regulatory and commercial milestone payments, plus royalties on global commercial sales. Both will conduct initial research and discovery activities for each target. After that, Abbvie is solely responsible for further development and commercialization.

The agreements provide $50 million up front for Harpoon and up to $50 million in a contingent milestone payment for the first patient treated with HPN-217 in a clinical trial. It provides a runway that McMahon said gives the company a solid path through its currently unpartnered programs.

“This transaction funds us into the second half of 2022,” McMahon said. “It’s significant capital.”

“Overall, we believe the combination of small size, extended half-life, and stable structure of the TriTAC platform positions [Harpoon] favorably within the highly competitive bispecific landscape,” SVB Leerink analysts noted Thursday.

That landscape is indeed competitive. In June, Amgen Inc. reported updated results from a phase I, first-in-human, dose-escalation trial of AMG-420, a BCMA-targeting bispecific T-cell engager (BiTE) molecule, in patients with relapsed/refractory multiple myeloma (r/r MM) at the American Society of Clinical Oncology meeting. In the study, 42 patients who had progression after at least two prior lines of treatment, including a proteasome inhibitor and an immunomodulatory drug, received AMG-420 at varying doses, 0.2 µg/day to 800 µg/day. Of the doses tested in that study, 400 µg/day was the maximum tolerated dose. The overall response rate at 400 µg/d was 70% (7/10). The median duration of response was nine months (range 5.8-13.6 months). Median time to response was one month, with 11 of 13 patients responding in the first cycle.

The first product for Harpoon, HPN-424, targets prostate-specific membrane antigen and is in a phase I trial for metastatic castration-resistant prostate cancer. Harpoon’s second product, HPN-536, targets mesothelin and is in a phase I/IIa trial for cancers expressing mesothelin, initially focused on ovarian and pancreatic cancers. In February, it priced its IPO of 5.4 million shares at $14 each. Harpoon (NASDQ:HARP) had a good day Thursday, closing up 6.15% at $15.35, while Abbvie (NYSE:ABBV) dropped barely below a percentage point, closing at $86.52.

The company name comes from the concept of tethering a T cell to an antigen, McMahon said.

“Like a harpoon with the barb on the end, it can snare something, like if a T cell comes by, it hooks and grabs it,” he added.

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