Innovation: First-in-class botanical cancer platform drug
Targeted Cancer(s): Phase II Hepatitis B (+) Hepatocellular Carcinoma
Leadership: Peikwen Cheng, CEO; Yung-Chi Cheng, PhD Co-founder; Shwu-Huey Liu, PhD Co-founder and Chief Scientific Officer (Click here to view our team)
Stage of Business: Raised $7M Series A financing
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.
YIV-906’s multi-target and synergistic mechanisms of action enhance the innate immune response in the tumor microenvironment (via neoantigens, 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).
The US FDA has granted YIV-906 two orphan drug designations for liver and pancreatic cancers. And China’s Ministry of Science and Technology is supporting YIV-906’s next trial as a “China National Major Project for New Drug Innovation”.
Unmet Medical Need
Heterogeneity in patients, tumor biology, and drug response make it difficult to have a single compound or anti-body treat cancer. Current therapies have modest response rates and serious toxicities. Rational combination strategies are needed that can improve patient response and quality of life in a meaningful way. A systems biology approach can lead to new breakthroughs.
Liver cancer is the 6th most common cancer with 840,000 new cases in 2018 and the 4th leading cause of cancer death worldwide. Hepatocellular Carcinoma (HCC) is the fastest rising cause of cancer-related death in the US and incidences have tripled in the US over the last four decades. HCC is the 2nd leading cause of cancer death in East Asia and sub-Saharan Africa. Hepatitis B (+) carriers are 200x more likely to get HCC. HBV (+) results in 60-80% of HCC cases worldwide. In China, 140 million people have HBV and over 400,000 have liver cancer. HBV (+) HCC cases are projected to grow annually in China until 2045.
The global first-line therapy for HCC is sorafenib. In HBV (+) HCC patients, the median overall survival is 10.2 months and progression free survival is 3.6 months. Serious adverse effects (80%) in sorafenib patients can lead to discontinuation (38%), dose interruptions (44%) and permanent discontinuation (11%). New treatments are becoming available, including lenvatinib which is approved as another first-line option in some countries, however their response rates, efficacy and safety profiles are insufficient.
YIV-906 is the only drug that is 1) an immune enhancer – potentiating innate and adaptive immune anti-tumor activity in the tumor microenvironment, and is 2) cytoprotective of the gastrointestinal tract from inflammation and speeds up tissue recovery. This systems biology benefit can lead to better patient outcomes and reduce the need for additional medications.
Yiviva is pioneering a new paradigm in polychemical, multi-target medicines and leveraging the US FDA’s pathway for Botanical Drugs – which opens up the untapped potential of complex mixtures. This new guidance allows for flexibility in manufacturing (CMC) and the ability for drug candidates, based on formulations with human usage (such as TCM), to move faster into the clinic.
Asset Profile & Development Plan
Proof of Concept and Safety: In clinical studies in +170 patients in liver, pancreatic, colorectal and rectal cancers, promising data suggests that YIV-906 can significantly increase patient survival for chemotherapy and radiation patients, and reduce serious Grade 3, 4 gastrointestinal side-effects to zero-to-minimal. Preclinical and clinical data have been published in journals including Science Translational Medicine, Scientific Reports and National Geographic.
Intellectual Property: Yiviva has a comprehensive portfolio strategy that includes patents, know-how, trade secrets and regulatory protections. Yiviva has licensed exclusive global rights for YIV-906 and pipeline candidates, its STAR Discovery Platform and mechanism-based quality control platform from Yale University.
Clinical Development Plan: In December 2019, Yiviva will initiate a double blind, randomized, Phase II clinical study for Hepatitis B (+) Hepatocellular Carcinoma using sorafenib +/- YIV-906 (potential first line therapy), with progression-free-survival as the primary endpoint. 125 patients will be enrolled across 20 institutions in four regions – US (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). Study will include liquid biopsies and biomarker research that may be predictive for future clinical studies.
Team: Yiviva is co-founded by Yale University and Dr. Yung-Chi Cheng. Dr Cheng has discovered four approved drugs, including the first drugs for Hepatitis B (lamivudine) and Cytomegalovirus (ganciclovir).