Synthesis Platform

Material access represents the critical barrier to facilitating active carbohydrate-based product development programs. To address this need, Ancora initially has focused on building a powerful and comprehensive set of carbohydrate synthesis technology solutions. The Ancora synthesis platform currently provides several key advantages to the carbohydrate-based discovery and development process, including:

• High purity molecules. Ancora is able to provide material that is both substantially higher in quality and more homogenous than can be achieved via either purification from biological sources or enzymatic synthesis.
• Lead candidate identification. Ancora’s synthesis platform provides access to discrete, well-characterized carbohydrate structures for early stage testing, which is not otherwise practical even with the state-of-the-art purification and analytical technologies.
• Enabling lead candidate optimization. Deliberate and rational changes to structures are essential to improving candidate characteristics during lead optimization. Utilizing its flexible chemistry solutions, Ancora is able to optimize lead carbohydrate candidate structures and is not limited to the use of purely natural carbohydrate sequences.
• Reproducible material production. Proper drug development requires access to material with consistent and controllable impurity profiles in order to minimize variability in pre-clinical and clinical testing. Ancora has developed highly reproducible in-house processes for the production of complex carbohydrates.
• Scalable material access. Ancora’s synthesis capabilities are able to generate material in quantities to support therapeutic development, from pre-clinical studies to the clinic. By contrast, proper scale-up of traditional purification and enzymatic processes can take years and often cannot meet the material demands to completely or rapidly support development.

Synthesis Technology Platform Components

Production of defined carbohydrates through chemical synthesis occurs in three distinct stages:

• first, production of functionalized building blocks;
• second, assembly of building blocks into an oligosaccharide; and,
• third, deprotection and purification of the synthetic carbohydrate.

Success in all three areas is required for the production of high purity, cost-effective products.

Building Block Technology

A functionalized building block is a basic monosaccharide that is modified with distinct chemical groups in order to direct proper assembly. The functional building blocks themselves need to be generated—typically, a starting material will undergo many chemical manipulations to allow for the incorporation of the desired protection pattern.

Ancora has developed building blocks that provide at least three key advantages supporting robust carbohydrate synthesis for commercial applications.

• Increased flexibility. Ancora has developed processes that support the generation of multiple building blocks from a small set of intermediates, enabling the synthesis of diverse complex carbohydrate molecules from a limited inventory of building blocks.
• Fewer intermediate stages. Ancora is designing novel synthesis pathways for functionalized carbohydrate building blocks using a dramatically reduced number of chemical manipulations, providing a cost and speed advantage to the company.
• Scale-up and process development capability. Ancora has developed processes for the production of building blocks on multi-kilogram scale with limited chromatography. Large scale building block capacity is important for advanced product development.

Assembly Technology

Ancora has developed and continues to advance assembly technologies based on solution and solid-phase methodologies. Each assembly method requires the efficient and selective combination of building blocks in an iterative process of elongation and differentiation.

Ancora has enabled the selection of appropriate building blocks and assembly methods in order to:

• Assemble defined complex carbohydrates. Ancora has demonstrated the capability to synthesize highly complex sequences of oligosaccharides up to 4 kDa MW in high purity. Ancora’s assembly methods provide products of high isomeric purity and allow the incorporation of modifications such as synthetic linkers, phosphorylation and sulfation, and reactive chemical handles for conjugation.
• Scale the synthesis of complex carbohydrates. Ancora has developed scalable processes for the production of synthetic oligosaccharides. Ancora has expertise in the design and execution of methods leading to highly crystalline intermediates and final products that enable progression to economical scale-up.
• Automate the assembly of complex carbohydrates. Ancora has advanced the automated assembly of carbohydrates utilizing proprietary instrumentation and solid-phase technology. Ancora’s automated assembly technology offers the ability to produce complex, discovery scale synthetic oligosaccharides more rapidly than solution-phase methods, and in a cost effective manner.

Deblock and Purification Technology

The final steps in the production of synthetic carbohydrates involve the late-stage molecule deprotection and final molecule purification. Ancora has developed numerous proprietary methods for the deprotection of synthetic oligosaccharides in high yield.

Further, Ancora has expertise in the purification of fully deprotected carbohydrates using a variety of chromatographic methods. Without the large number of contaminating compounds often present in material isolated from biological sources, synthetic material can be obtained in high purity with little to no contaminating carbohydrate sequences.