Seattle Genetics will partner with Pieris Pharmaceuticals to develop bispecific immuno-oncology treatments through a collaboration that could generate up to $1.2 billion-plus for Pieris, the companies said today.

The companies would work to create antibody–anticalin fusion proteins for solid tumors and blood cancers by combining Seattle Genetics’ cancer targets and tumor-specific monoclonal antibodies—developed through its work on antibody–drug conjugates—with Pieris’ proprietary Anticalin® technology platform, which the company has applied toward treatments for cancer as well as respiratory and other diseases.

The bispecific drug candidates to be developed will be designed to enable the patient's immune cells to specifically attack tumors, the companies said. Pieris and Seattle Genetics agreed to study multiple antibody–Anticalin fusion proteins during the collaboration’s research phase, with Seattle Genetics retaining an option to select up to three therapeutic programs for further development.

However, Pieris may opt into global codevelopment and U.S. commercialization of the second program before the launch of a pivotal trial, in return for sharing in global costs and profits 50/50 with Seattle Genetics—which agreed to solely develop, fund, and commercialize the other two programs.

Seattle Genetics agreed to pay Pieris $30 million upfront, up to $1.2 billion in payments tied to achieving milestones across all three planned product candidates, plus tiered royalties on net sales up to low double-digits.

“This partnership leverages our cancer targets and tumor-specific antibodies to explore multiple novel bispecific combinations, with the goal of developing targeted therapies that improve outcomes for people with cancer,” Dennis Benjamin, Ph.D., svp of research at Seattle Genetics, said in a statement. “Pieris’ Anticalin technology and antibody–Anticalin bispecific approach are intended to overcome the limitations of currently available immuno-oncology products.”

Engineered Lipocalins

According to Pieris, anticalin proteins are engineered lipocalins, endogenous low-molecular-weight human proteins typically found in blood plasma and other body fluids that naturally bind, store, and transport a wide spectrum of molecules.

Anticalin proteins, as with the 12-member human lipocalin class, are defined by a four-loop variable region and a beta-barrel backbone that form a pliable cup-like binding pocket. Within the loops and ligand-binding areas of the beta barrel, anticalin proteins contain diverse amino acids while maintaining the lipocalin structure.

Pieris’ most advanced anticalin is PRS-080, a Phase Ib/IIa hepcidin antagonist co-developed with Aska Pharmaceutical and indicated for anemia, to which Pieris holds rights in major markets outside Japan.

However, Pieris has several immuno-oncology anticalins in development, led by PRS-343, a Phase I bispecific fusion protein combining a CD137-specific anticalin with a HER2-targeting antibody. Two other cancer anticalins are in preclinical phases: PRS-342, which combines a CD137-specific anticalin with a GPC3-targeting antibody; and PRS-332, a novel programmed cell death protein 1 (PD-1)-based bispecific, consisting of an anti-PD-1 antibody genetically linked to an anticalin targeting an undisclosed checkpoint.

The collaboration with Pieris is Seattle Genetics’ second big-money deal aimed at expanding its oncology pipeline in recent weeks. On January 31, the company said it plans to acquire Cascadian Therapeutics  for approximately $614 million, which would add to the buyer’s pipeline Cascadian’s Phase II breast cancer candidate tucatinib (ONT-380).

Seattle Genetics suffered a cancer-related setback in June, when it terminated a Phase III trial of cancer candidate vadastuximab talirine (SGN-CD33A) in frontline older acute myeloid leukemia (AML) after reviewing unblinded data indicating a higher rate of deaths, including fatal infections, in the vadastuximab talirine arm compared with the control arm. Seattle Genetics also halted enrollment in all other clinical trials assessing the antibody–drug conjugate targeting the CD33 protein.

Seattle Genetics is the third biopharma with which Pieris is partnering to develop immuno-oncology anticalins. Pieris’ other two such collaborations are with Servier (up to €1.7 billion [$2.083 billion] launched in 2017) and Roche (up to $409 million, launched in 2015).

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