preclinical pipeline

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NOXXON’s discovery group is constantly evaluating targets and developing new Spiegelmers. Noxxon’s publicly disclosed discovery stage programs are listed below:

CandidateNOX-G15
TargetGlucagon
DescriptionExcessive secretion of glucagon – a functional insulin antagonist – significantly contributes to hyperglycemia in type 1 and type 2 diabetes mellitus. The inhibition of glucagon is therefore a promising mechanism for the treatment of diabetes with a mode of action distinct from existing therapies. NOXXON’s glucagon-specific Spiegelmer NOX-G15 binds to glucagon and inhibits its action in vitro at low nanomolar concentrations. A single injection was also found to reduce hyperglycemia after an intraperitoneal glucose challenge in mouse models of type 1 and type 2 diabetes mellitus.

CandidateNOX-S93
TargetS1P (sphingosine-1-phosphate)
DescriptionS1P is a signalling sphingolipid that acts through five G-protein coupled receptors and regulates angiogenesis, vascular stability and permeability as well as trafficking of certain cells of the immune system. By specifically neutralizing S1P itself, NOX-S93 inhibits signaling of S1P through EDG1 and EDG3 (others not tested yet) with low nanomolar affinity in cell based assays. As expected, NOX-S93 induced transient lymphopenia by retarding lymphocytes in lymphoid organs in a proof-of-mechanism study in mice. Target indications of NOX-S93 are angiogenesis in cancer, ocular diseases as well as autoimmune disorders.

CandidateNOX-D19
TargetComplement Component C5a
DescriptionThe complement system is an effector mechanism of the innate immune system. Complement component  5a (C5a) is part of the terminal complement cascade and generated as a small glycoprotein of 74 amino acids by cleavage of C5. It is a potent inflammatory mediator that may lead to organ damage when excessively activated, such as in sepsis. Its role and activity in other acute inflammatory episodes has been published in respect to colitis, arthritis, SLE, and other rare autoimmune diseases.
NOX-D19 inhibits the C5a-induced chemotaxis of a C5a receptor-expressing cell line at picomolar concentrations. In an experimental murine model of polymicrobial septic shock NOX-D19 prolonged survival and reduced liver and kidney failure.