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Sanofi-Aventis Taps Pieris for Anticalin Drug Development for €3.5M

Deal initially covers two targets and up to €44.5 million in milestone fees per product. Sanofi-Aventis inked a deal with Pieris under which the latter will use its Anticalin technology to discover drugs against two targets for €3.5 million (about $4.73 millio

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Deal initially covers two targets and up to €44.5 million in milestone fees per product.

Sanofi-Aventis inked a deal with Pieris under which the latter will use its Anticalin technology to discover drugs against two targets for €3.5 million (about $4.73 million) up front. Anticalins reportedly have the potential to overcome some constraints of mAbs. The collaboration includes research funding, success-based fees, and the option for four additional targets.

For each new product, the agreement could earn Pieris up to €26.5 million (approximately $35.75 million) in development milestones for the first therapeutic application and €18 million (roughly $24.29 million) in commercial milestones. The firm would obtain further milestones if the same product is developed in different applications. Sanofi-Aventis and Sanofi Pasteur will have exclusive marketing rights worldwide for all such products. Payments will also include tiered royalties on sales resulting from the collaboration.

“Sanofi-Aventis’ basic objective of finding new solutions to address patients’ needs is furthered in this collaboration by exploiting innovative technology which focuses on some of the fundamental mechanisms of disease processes,” comments Leopold Bertea, vp of the Scientific Core Platform, Biologics Center at sanofi-aventis. “Pieris’ Anticalin technology will allow sanofi-aventis to take a more comprehensive approach to developing targeted therapeutics, as we believe the Anticalin technology will complement our existing suite of more conventional technologies.”

Anticalins 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. The defining attributes of the 12-member human lipocalin class, and therefore Anticalins, are a four-loop variable region and a rigidly conserved beta-barrel backbone, which, together, form a pliable cup-like binding pocket. Anticalins contain rationally diversified amino acids within these four loops and ligand-binding areas of the beta barrel while maintaining the integrity of the lipocalin structure.

This diversity has yielded a drug class that provides specificity and affinity against a wide spectrum of targets, exhibits the safety of an endogenous protein performing an endogenous function, and is durable, creating greater flexibility of formulation and delivery, Pieris explains. Additionally, anticalins tightly bind a target as a monovalent molecule, overcoming the complications of multivalent binding approaches, when agonist receptor cross-linking is therapeutically counter-productive, the firm adds.

The company’s suite of proprietary phage display libraries has been created by rationally diversifying the lipocalin regions that are responsible for ligand binding. Different libraries are applied to different types of targets. Once defined, a novel Anticalin can be produced in a bacterial expression system.

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Related questions

01How stable is the antibody?

A crucial question often addressed during preclinical development focuses on the in vivo stability of therapeutic antibodies. Increasing the half-life of a therapeutic antibody has several benefits ranging from higher treatment efficacy to increased advantages for the patients who will have a fewer number of therapy sessions and a reduced cost. Given these compelling benefits, following the identification of therapeutic antibodies with the desired specificity, developers usually subject them to a refinement step to increase their stability. This process is often hindered by the lack of reliable experimental tools to predict the half-life of antibodies in patients. The major hurdle of using mouse models to predict antibody stability in the serum lies in the way immunoglobulin proteins are processed by the organism. In mammals, most proteins circulating in the serum undergo constant uptake by endothelial cells and are routed through the endosomes to the lysosomal compartment for degradation. In the endosomes, immunoglobulin G (IgG) proteins are recognized and bound by a transmembrane protein, called the neonatal Fc receptor (FcRn), which mediates their recycling to the plasma membrane and subsequent release back into the serum. As a result, the half-life of IgGs are significantly extended by this mechanism. Since most therapeutic antibodies belong to the IgG class, this recycling system is very relevant for their relative stability in the body. Remarkably, the relative affinity between IgGs and FcRn is extremely disparate between different species, with the mouse receptor showing a much higher affinity than its human counterpart.

Source: www.genengnews.com ↗
02Undruggable or unscreenable?

Another obstacle to discovering new PPI inhibitors is the lack of libraries designed to hunt for them, points out Philippe Roche, PhD, senior scientist at the Integrative Structural and Chemical Biology team at the Cancer Research Center of Marseilles, France. “If you screen PPIs using libraries that were designed for kinases or GPCRs, that’s why you don’t get a lot of good results,” he says. To that end, his group began assembling a library focused on orthosteric inhibitors of PPIs. The result was 2P2Idb, a hand-curated, structural database cataloguing orthosteric inhibitors of PPIs for which the interface had been 3D characterized. From analyzing these known PPI inhibitors, and what structures they had in common, Roche and his colleagues developed a model to predict whether compounds would likely inhibit PPIs. Using this method, 2P2Idb creates an enriched screening library that dramatically increases the hit rate compared to standard libraries. Having proven their success with a small library of 1600 compounds, they are in the process of expanding the library to 10,000 compounds. Once that’s published, “the idea is to make this library available to labs around the world,” Roche says. “We will provide the library free of charge for people to be able to screen PPI targets.”

Source: www.genengnews.com ↗
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Peptide Therapy Guide Editorial Team

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