The microbiome, the genetic material contained by our symbiotic bacteria, contains roughly 2 million genes, 100-fold more than our human genome. Indeed, the microbiota that make up our bacterial symbiotes that share the human body outnumber our human cells by at least 10-fold.
We need our symbiotic microbiota. They perform essential catalytic tasks associated with simple dietary processing to complex immunological modulation and neurological function. Thus, we do not want to harm them, as they are far mutually protective of us, in the same way that we are protective of them.Our goal is the non-lethal, selective, and potent modulation of bacterial factors that impact human disease. We have achieved this goal, and have established a fundamentally new drug discovery paradigm that opens the door to the two million bacterial genes in the human microbiome.
Most importantly, all of our lead chemical entities are non-lethal – they kill neither bacterial cells, nor human intestinal or other cells. Thus, we have achieved what others have unsuccessfully attempted – to control, rather than eliminate, our bacterial symbiotes. In several models of drug-induced toxicity, our reagents show powerful effects, significantly reducing GI damage.
Utilzing our core technology to we continue to identify additional, "drugable" bacterial enzymes that not only reduce drug toxicity but modulate human disease.
Our initial program focuses on alleviating the toxicity associated with chemotherapeutics essential for the treatment of cancer. Toxicity of these drug classes is caused by the reactivation of therapeutic metabolites in the GI by the resident bacteria. In fact, we have shown that a single enzyme, bacterial beta-glucuronidase, is responsible for this dose limiting toxicity. Our novel and proprietary lead candidates selectively and potently inhibit this bacterial enzyme, which is widely expressed in the intestinal symbiotic bacteria. Candidates are at least 10,000-fold more selective for this bacterial enzyme than the human orthologous enzyme. Our potency is lower nanomolar on-target with a clearly established mechanism of action.
This program is currently in lead series selection, with the focus on moving a lead candidate into preclinical development and IND enabling studies. The program is, in-part, funded by the US National Cancer Institute.
Long-term use of NSAIDs can lead to toxic effcts in the lower GI causing ulcers, irritable bowel, and intestinal inflammation. Bacterial beta-glucuronidase has been implicated in this toxicity and animal models have shown that inhibition of this bacterial enzyme reduces NSAID side-effects.
This program is a follow-on to our Chemotherapy Adjunct. Through the work already in-progress, a lead series will be identified for further optimization specific to this indication.