YIV-906

Innovation: Therapeutics—first-in-class botanical cancer platform drug
Targeted Cancer(s): Liver cancer
Scientific Leadership: Yung-Chi Cheng, Ph.D.; Shwu-Huey Liu, Ph.D.
Stage of Project: Phase II clinical trial about to commence; orphan drug designations granted by the U.S. Food and Drug Administration (FDA)

YIV-906 is a botanical cancer drug that can potentiate anti-tumor activity for immunotherapy, chemotherapy and radiation therapies—and could become the backbone drug for future cancer regimens. Its multi-target and synergistic mechanisms of action enhance the innate immune response in the tumor microenvironment (via neoantigens and M1 macrophages), while also cytoprotecting the gastrointestinal tract by reducing inflammation (via IL-6, NF-KB, COX2 iNOS) and speeding up tissue recovery by promoting progenitor and stem cell growth (via WNT).

• Heterogeneity in patients, tumor biology and drug response make it difficult to have a single compound or antibody treat cancer. Current therapies have modest response rates and serious toxicities. Hence, rational combination strategies are needed that can improve patient response and quality of life in a meaningful way. And a systems biology approach can lead to new breakthroughs.
• Liver cancer is the sixth most common cancer, with 840,000 new cases in 2018 and the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC), in particular, is the fastest rising cause of cancer-related death in the U.S., where incidences have tripled over the last four decades.
• Hepatitis B virus (HBV) carriers are 200 times more likely to get HCC than the average person, and HBV-positive individuals results in over 60% of HCC cases worldwide.
• The global first-line therapy for HCC is currently sorafenib. But serious adverse effects (80%) in sorafenib patients can lead to discontinuation (38%), dose interruptions (44%) and permanent discontinuation (11%). Reducing those serious adverse effects could have profoundly beneficial therapeutic impacts.

• YIV-906 is the only known drug candidate that has been shown to be (1) an immune enhancer, potentiating innate and adaptive immune anti-tumor activity in the tumor microenvironment, and (2) cytoprotective of the gastrointestinal tract from inflammation, allowing for an increased rate of tissue recovery.
• The proprietary formulation’s systems biology benefits can lead to better liver cancer patient outcomes and reduce the need for additional medications.
• A combination treatment, consisting of an existing drug, such as sorafenib, together with YIV-906, could become the new first-line therapy.

• Proof of Concept / Safety and Tolerability:In clinical studies of over 170 patients in liver, pancreatic and colorectal cancers, promising data suggests that YIV-906 can significantly increase patient survival for chemotherapy and radiation patients and reduce serious Grade 3 and 4 gastrointestinal side-effects to zero-to-minimal; pre-clinical and clinical data have been published in multiple highly cited journals, including Science Translational Medicine and Scientific Reports, as well as National Geographic
• Intellectual Property:A comprehensive portfolio is held that includes patents, know-how, trade secrets and regulatory protections; exclusive global licensing rights for YIV-906, pipeline candidates and their mechanism-based quality control and drug discovery platforms have been obtained
• Clinical Development Plan:A double blind, randomized, Phase II clinical study whose protocol has been approved by the FDA and other pertinent national regulatory bodies is soon to be underway for HBC-positive HCC patients using sorafenib with YIV-906, with progression-free-survival as the primary endpoint; 125 patients will be enrolled across 20 institutions in four regions: the U.S. (led by Memorial Sloan Kettering), China (led by National Cancer Center), Hong Kong (led by Queen Mary Hospital) and Taiwan (led by Taipei Medical University)