Altus® applies its proprietary protein crystallization technology toward developing innovative protein therapeutics for chronic gastrointestinal (GI) and metabolic diseases. This technology, and our strategy of applying it to existing, well-understood proteins that would ordinarily be rendered ineffective by the harsh gastrointestinal tract, allows us to overcome many of the obstacles that have blocked the commercialization of high-value, orally delivered protein therapeutics for many years. Unlike these large molecule therapeutics, small molecule drugs have been delivered orally in the crystalline state for more than a hundred years. This state provides significant stability against temperature and pH in the stomach, and therefore allows the active drug product to reach the intestine where it can be absorbed into systemic circulation, whereupon it is able to go on to exert its therapeutic effect. Conversely, protein therapies have not been afforded the use of the crystalline state for two main reasons. First, protein crystallization is significantly more complex than small molecule crystallization and for this reason it has not historically been a commercially scalable process. Secondly, it is widely believed that even if proteins could be crystallized and were able to pass through the degradative environment of the stomach (which functions to digest proteins and fats amongst other things), the complexity of the molecule would preclude it from being absorbed through the intestinal wall and into systemic circulation. Altus' technology allows the company to overcome the first challenge as it is the first technology that allows commercially scalable bulk protein crystallization of protein therapeutics. To circumvent the second challenge, Altus strategically focuses on diseases that can be treated with therapies that exert a therapeutic effect in the lumen of the GI tract or which create a gradient across the intestinal wall to facilitate removal of toxic substances from the blood stream through enterocirculation.

Our protein crystallization technology enables a robust, reproducible, and large scale commercial process for the production of protein crystals. Our approach is fundamentally different than crystallization for x-ray crystal diffraction as we are less concerned with the crystal size and shape normally required for structural analysis and more concerned with high reproducibility, scalability, and stability. These variables are critical in the manufacture of a commercializable product. Like any other drug product, highly reproducible and scalable production methods ensure a consistent product that can be produced at levels appropriate to meet consumer needs. Additionally, in this situation, stability is as crucial ex vivo on the shelf as it is in vivo. Obviously the shelf stability of the product and the conditions under which the product is stored are very important, however, due to the proposed mechanism of action of our products, in vivo stability against the harsh environment of the GI tract is also critical. In both situations, protein crystals are inherently more stable than their non-crystalline counterparts and for this reason they offer distinct advantages over native protein molecules in either the dried or suspended state.

An extension of our proprietary technology allows us to further enhance the stability of the crystal by cross-linking the molecules within the crystal lattice, thereby creating stronger intramolecular bonds and adding significantly greater stability. By optimizing the formulation we are able to exert control over where a product is going to be most active and therefore most effectively exert its therapeutic effect. In many cases, high in vivo stability against proteolytic and acid degradation is very important as it allows the product to survive the harsh, digestive environment of the stomach and move into the small and large intestines to demonstrate an effect.

Altus' strategic focus is on diseases that can be treated by a drug that exerts a localized, therapeutic effect on the intestinal wall or within the lumen of the GI tract. Research on GI and metabolic diseases shows that many of these diseases and disorders may benefit from protein-based therapies if delivered to the lumen of the GI tract. Altus has identified numerous proteins that may effectively treat these types of diseases and believes that therapeutic protein crystals of this type have distinct advantages, as they are more readily delivered to the site of action, may have a more significant therapeutic effect, and have may an increased safety profile.

Altus' technology and strategic focus may allow significant improvements in the treatment of many GI and metabolic diseases that are currently lacking adequate effective treatments. Protein crystallization acts as a platform for enabling the oral delivery of therapeutic proteins to the ideal site of action while offering the opportunity for improved efficacy and enhanced treatment options.