TECHNOLOGY
OUR SCIENCE
Our research has generated a critical understanding of the role of drug metabolizing enzymes and transporters and gut microbiome on the systemic and gastrointestinal (GI) exposure of drugs and their metabolites, dietary components and toxins, and endogenous substrates majorly metabolized in intestine via the involvement of hepatoenteric, enterohepatic, enteroenteric and local recycling mechanisms. To protect the gut against drug-induced toxicities and the imbalances of endogenous substrates leading to gut diseases/disorders, the systemic and intestinal exposure of these compounds and their metabolites needs to be tightly controlled. Sanarentero technologies aim to protect the gut by maintaining or enhancing the detoxification ability of enterocytes and colonocytes or modulating the metabolic function of gut microbiome by inhibiting beta-glucuronidases or introducing newer metabolic functions for drug detoxification while maintaining healthy gut microbiome.
CLINICAL PROBLEM
Irinotecan-induced Severe Delayed Onset Diarrhea
Irinotecan is a key chemotherapeutic drug for various metastatic cancers including colorectal, gastric, non-small cell lung, pancreatic, breast, and others. It is often the drug of last resort for recurrent and refractory diseases when used alone or in combination with other therapeutic agents. IR treatment shows dose-limiting serious and sometimes life-threatening toxicities of neutropenia (decrease in the absolute number of neutrophils to < 500-1500 cells/mm^3) and severe and delayed onset diarrhea (SDOD), induced by SN-38 (the active metabolite of Irinotecan) in about 15%-40% of the patients. The latter requires hospitalization resulting in increased cost by $6600-8,000/patient per episode, and interruptions, delays, and even cessation of irinotecan therapy.
OUR PRODUCT PIPELINE
PRODUCT PIPELINE
OUR SCIENCE
Although the use of granulocyte colony-stimulating factors and broad-spectrum antibiotics can effectively manage irinotecan-related neutropenia, the management of SDOD is still challenging as irinotecan-induced SDOD is inconsistent, unpredictable, non-cumulative, dose-dependent, with wide inter-patient and intra-patient variability. In patients with mild to moderate (grade 1 or 2) diarrhea, antibiotics, and antidiarrheal drugs, such as loperamide or octreotide, can effectively manage the symptoms.
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However, these treatments are associated with many gastrointestinal side effects and unsatisfactory outcomes. In patients with more than grade 2 diarrhea, irinotecan therapy is routinely withheld and leads to undesirable dose reduction, delay, or cessation of irinotecan therapy, as the patients need to be free from diarrhea for at least 48 hrs without antidiarrheals before the next irinotecan therapy. Moreover, these drugs do not prevent the underlying progression of irinotecan-induced intestinal damage, and irinotecan-induced SDOD remains dose-limiting toxicity in both adult and pediatric cancer patients.
Since the accumulation of SN-38 is responsible for the dose-limiting gut toxicity of IR, there is an urgent need to effectively detoxify SN-38 at the site of toxicity (i.e., terminal ileum and colon) for optimal utilization of irinotecan therapy in the clinics. Sanarentero is currently developing two unique technologies to address this clinical problem.
