Technologies

Our Technologies

We’ll do whatever it takes to generate new drugs for tuberculosis therapy. These drugs are either chemicals or biologicals, e.g., antibiotics or human antibodies. Traditionally, the discovery of either one of these medicines has required large teams, but recently, dedicated contract research organizations have taken over important parts of the processes. This allows us to concentrate on our core competencies that we have assembled in our company.

Antibodies

Austrianni has unrestricted access to the powerful antibody discovery platform developed by the California company Trianni. This platform features the complete diversity of human antibody variable domains, which undergo natural V(D)J recombination and somatic hypermutation. Using this platform, Austrianni isolates fully human antibody therapeutics for the treatment of tuberculosis, with emphasis on multidrug resistant tuberculosis.

These antibodies may work
in two different ways:

1.

Redirect the immune system of the host (patient).

In the host-directed therapy approach, we modulate a signaling pathway in the cells of the patient. Such signaling pathways are important in the communication between cells. The signal is received by a receptor on the surface of a cell and instructs the cell how to behave, i.e., which molecules to produce, which functions to perform, and where to go. Because Mycobacterium tuberculosis causes an overshooting signaling response in infected cells, we aim to dampen it by means of monoclonal antibodies.

2.

Hit the pathogen (bacterium) directly.

In the pathogen-directed approach, we are developing antibodies to structures on the surface of the bacterium and to the proteins it secretes. We generate antibodies that target specific proteins, but we do not limit ourselves to antibodies to single structures of the bacteria. In a comprehensive approach, we generate antibodies against all surface structures and all proteins that are released by the bacteria.

Small Molecules

There are many enzymes that Mycobacterium tuberculosis cannot live without, and several antibiotics exploit this fact. Traditionally, antibiotics were found by testing large collections of microorganisms, or large collections of chemicals, for their ability to interfere with bacterial growth. Or chemical libraries were tested against an isolated target. In either case, only a tiny fraction of the vast chemical space of drug-like structures, estimated to consist of 10⁶³structures, can be covered.

Today, the three-dimensional structures of many important proven or putative targets have been solved in requisite detail, either by X-ray diffraction or cryo-electron microscopy. This enables the computational screening of large virtual compound libraries. Of course, these libraries are valuable only if the selected compounds can also be synthesized within a reasonable time, so that they can be ‘wet-lab’ tested against the isolated target or in an assay of biological function.

To date, over 500 million compounds have been collected in a virtual library. All compounds of this collection can be chemically synthesized from smaller compounds on demand by a commercial supplier. From this large virtual library, we computationally select over hundred best-fit compounds that are then tested in our biological tests.

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