Complex sugars play a vital role in cellular function and disease.

Sugars, together with DNA and proteins, are critical molecules that regulate biological processes and pathways in the human body. Complex sugars play a fundamental role in most basic biochemical functions such as cell growth and migration, self/non-self immune recognition, and cell-to-cell communication, in addition to serving as key modulators of protein activity. Because of their role in the regulation of biological activity, sugars play a fundamental role in the cause and treatment of many diseases as well as in drug action.

Complex sugars exist within, on the surface of, and between cells, where they are attached to proteins, lipids, and other biologic molecules. The location of a complex sugar determines the distinct function that it performs. For example, complex sugars “coat” the surfaces of virtually all cells. Cell surface sugars are critical for proper cell function and may act alone or in conjunction with proteins to regulate cell growth, death, or the future definition of a cell. Complex sugars at the surface of cells also influence the efficacy and side-effect profile of drugs, which target these areas. Complex sugars located between cells help cells communicate with one another to orchestrate complex biologic processes. For example, tissue generation, wound healing, and immune responses to viral infection are all biological processes which are regulated by sugars. Complex sugars coating proteins and other biologic molecules further influence how long the drug remains in the body and the specific activity that it performs. The sugars that coat a protein thus “fine-tune” the protein’s activity and provide an additional level of biological control. Understanding where sugars are found in the body, as well as their role in selected therapeutics thus creates significant opportunities for complex sugar-based drug discovery and development.

While scientists have long recognized that sugars are important, the chemistry and function of sugars have remained a virtual “black box” for many years due to the technical and analytic challenges associated with sequencing complex sugars and the dramatic structural complexity and information density contained in sugars. Unlike DNA, which can combine to produce 256 four-unit structures, and proteins, which can form approximately 160,000 potential four-unit structures, sugars can theoretically manifest in more than 5.3 million combinations. As a result, the development of sugar-based drugs to date has been through more of a “trial and error” approach.

Momenta opens up a new frontier in drug development.

Momenta has developed an integrated technology solution that addresses many of the challenges associated with creating drugs based on complex sugars. Our technology combines multiple proprietary enzymes and reagents, sugar-based analytic techniques, and mathematical methods for integrating data to converge on unique structural solutions, identifying specific sugar sequences.

Our technology has enabled us to rapidly sequence complex sugars in a matter of minutes to hours --- a process which previously took years. Our technology has the following features:

Through internal patent filings and exclusive licensing arrangements, Momenta has assembled a broad estate of patents and applications related to its technology and pipeline products.

Demonstrating the power of Momenta's technology

Momenta’s work with low molecular weight heparins (LMWHs), which are commonly used as anti-coagulants, provide a strong demonstration of the power of our technology and expertise. Heparins exist as heterogeneous complex mixtures of sugar chains of varying length and varying sequence. Previously, technology did not allow for the precise identification, isolation, and characterization of the various chemical structures which constitute these complex mixtures. We believe that our technology enables detailed descriptions of various heparin products. We have leveraged this understanding to pursue two distinct kinds of product opportunities. By being able to both identify the sugar structures which make up heparin and relate them to biological function, we believe we will be able to design generic versions of complex sugar-based drugs and also rationally engineer improved versions of sugar-based products to address specific unmet needs in particular markets.

Non-characterized low molecular weight heparin

Enabling Generic Complex Drug Products

Under FDA guidelines, generic versions of marketed products must demonstrate that they have the same active ingredients as the innovator product. Typically, this can be completed through analysis which does not require large-scale clinical trials. While the standard of demonstrating the same active ingredients is relatively straightforward for small molecule drugs, it is inherently more difficult to define active ingredients for drugs which exist as complex mixtures. Our ability to sequence and analyze complex sugar mixtures has allowed us to study the many sugar structures in heparin, for example, and develop a process for making a generic version that we believe will meet the FDA requirements for generic approval.

Characterized low molecular weight heparin

Designing Improved LMWHs

We are leveraging our core technology to rationally design drugs, and enhance certain structures which contribute to optimal biological function. M118 is a LMWH that we rationally designed to provide improved anti-clotting activity and flexible administration to treat patients with ACS. To design M118, we utilized our proprietary analytic methods and enzymes, together with our ability to sequence the complex sugar chains within heparin starting material, to identify the sugar sequences responsible for anti-clotting activity. We then used our proprietary enzymes to precisely cut the longer chains of heparin in specific locations to develop a drug candidate containing the critical structures in an optimal arrangement to address certain unmet medical needs in ACS. For example, by strategically engineering the specific structures that bind to key coagulation factors, we believe we have created a molecule which can be fully reversed and monitored more effectively than currently available therapies.

Rationally engineered low molecular weight heparin