BioWorld Today Correspondent

Pieris AG is banking 7 million (US$10.1 million) up front and could earn up to 200 million more in milestone payments and research funding from a discovery deal with Daiichi Sankyo, based around its anticalin protein scaffold technology.

It's the third such deal that Pieris, of Freising, Germany, has entered within the past seven months, following similar target-based discovery agreements with Takeda San Francisco Inc., a subsidiary of Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, and with Paris-based Sanofi Aventis Group and its vaccines arm Sanofi Pasteur. It also has an ongoing discovery and development agreement in ophthalmology with Allergan Inc., of Irvine, Calif.

Under the new agreement, Pieris will identify anticalins that bind two targets supplied by Tokyo-based Daiichi Sankyo. The latter firm will take on development of the molecules during the preclinical research phase and will retain worldwide marketing rights. Pieris would gain what it termed "tiered mid- to mid-high single digit" royalties on any commercial products resulting from the alliance.

Pieris is neither disclosing the nature of the targets nor the disease areas involved in the agreement. But its CEO, Stephen Yonder, noted that it does not entail exclusivity within any particular field. "We don't want to cordon off too much of any area for any one partner," he told BioWorld Today.

Anticalins are engineered derivatives of lipocalins, endogenous extracellular proteins involved in numerous biological functions, including receptor binding and the transport of small hydrophobic molecules. The molecules' binding sites, which consist of four peptide loops attached to a beta-barrel scaffold, can be altered by site-directed mutagenesis to yield a large repertoire of ligand binders with differing specificities.

Their small size (a native anticalin has a molecular weight of 20 kilodaltons) is expected to offer superior tissue penetration to that of monoclonal antibodies and to offer easier manufacturing as well.

"We can produce in a whole range of bacterial systems, and we're getting some pretty good titers," Yoder said. Yields of 9 to 10 grams per liter have been achieved in non-optimized processes, he said.

The half-life can be optimized in several ways as well. "We have lots of opportunities to fine-tune the half-life so that it's fit for purpose," Yoder said. In addition to standard pegylation, Pieris is experimenting with protein-based stabilization methods. It is also experimenting with alternative delivery methods, including a dry-powder formulation of PRS-060, a molecule which binds Interleukin-4 receptor alpha and is in development for asthma.

So far, only one anticalin has entered the clinic. PRS-050, which binds vascular endothelial growth factor (VEGF), is undergoing a Phase I trial in patients with solid tumors. Although the study, which will report fully in the second half of this year, is focused primarily on evaluating the drug's safety and pharmacokinetic (PK) profile, it will also include an analysis of cancer biomarkers, in order to provide some indication of efficacy.

So far, the data are positive. "The PK [data] from this trial should allow us to dose on a biweekly basis. It's exactly where you need to be to be able to play in the oncology space," Yoder said.

A second molecule, PRS-110, which binds the oncology target cMet, could enter the clinic next year.

The up-front payment from Daiichi will extend Pieris's cash runway by at least another year, to three years, although the company has yet to decide how it will invest the new money.