Yiviva Brings Botanical Cancer Drug Deeper Into Clinic | 05/25/2021
VANCOUVER, British Columbia – Yiviva Inc., a pharmaceutical company focused on the development of botanical drugs, has advanced its lead candidate into an international Phase IIb trial for liver cancer and has moved closer to an application via the little used botanical route from the FDA and a similar route in China. The company’s lead candidate, YIV-906, is intended for use in immunotherapy, chemotherapy and radiotherapy.
With YIV-906, Yiviva is working on the development of a product capable of minimizing the number of drugs that cancer patients must take by modulating their immune and inflammatory responses. The results of the first studies, which have so far reached around 170 patients with liver, pancreatic, colorectal and rectal cancers, are promising, says Peikwen Cheng, co-founder and CEO of Yiviva.
“We developed it from an extract of four herbs, four very common herbs, licorice, peonies, dates and a skullcap,” Cheng said. BioWorld. “We drew on what was known and based on how we source and how we treat, we created a product that can now strengthen the immune system, cytoprotect the (gastrointestinal tract) and lead to regeneration fabrics.”
YIV-906 is an immune system modulator that has been shown to enhance anti-tumor activity in a wide range of cancer treatments by stimulating the immune response in the tumor microenvironment. It also cytoprotects the gastrointestinal tract to reduce inflammation and side effects and accelerates tissue regeneration by promoting the growth of progenitors and stem cells.
The researchers behind Yiviva have spent the past 20 years building platforms to develop systems biology drugs with a particular focus on diseases often associated with aging.
Single chemical drugs or single antibodies are limited in what they can do on their own, especially with complex diseases. This means that patients have to take several drugs at the same time and that these drugs have very targeted effects.
“When we look at cancer treatment, we believe that the next generation of cancer treatment will go beyond the tumor microenvironment,” said Cheng. “The goal is to improve the survival and quality of life of patients.”
Yung-Chi Cheng, Henry Bronson professor of pharmacology at Yale University and co-founder and president of Yiviva, began his research on plants in 2000. As a professor of pharmacology, he discovered and patented drugs in small molecules, especially for hepatitis B, and began to tackle the heterogeneous causes of the disease by hitting multiple targets at once.
Yiviva was founded in 2015 after being separated from Yale University to build on previous research. The company has developed three key platforms for drug discovery and production. The first is its signal transduction activity and response (STAR) drug discovery platform to design drugs with sophisticated mechanisms of action; the second is a quality control platform based on mechanisms to ensure consistency from batch to batch; and the third is a symbiotic microbiota for agricultural resources and a technological platform to ensure a scalable and quality supply of raw materials.
The furthest from the clinic among the company’s programs, YIV-906 is the subject of a first-line, randomized, placebo-controlled phase IIb study in combination with Nexavar (sorafenib, Bayer AG), a multi-kinase inhibitor, for the treatment of hepatocellular carcinoma. The company aims to recruit 125 patients at 20 sites in four regions: the United States, Mainland China, Hong Kong and Taiwan. The first patient was recruited in April 2020. The primary endpoint is to assess patients’ progression-free survival, while secondary endpoints include safety, quality of life assessments and some measures of clinical efficacy.
Other Yiviva products will target equally complex diseases. YIV-111 is an anti-inflammatory, anti-oxidant, and antiviral drug targeting pulmonary fibrosis, cancer pneumonia, and COVID-19 pneumonia. YIV-006 is a cytoprotector and regenerative drug for inflammatory bowel disease. YIV-201 has multiple mechanisms of action to target hepatitis C. All of these drugs are in preclinical development and are believed to generally target disease progression.
“We think about a patient’s journey and their life cycle and how we can treat them,” said Peikwen Cheng.
Yiviva’s goal is to combine metabolomics, systems biology and bioinformatics to accelerate drug discovery and develop products evaluated based on the botanical drug regulatory pathways of the US FDA and the China National Medical Product Administration.
“In the past, there has always been a black box around trying to understand these botanical drugs because, by themselves, they are complex mixtures,” Cheng said. “They’ve been in use for hundreds or thousands of years, but they’re a bit of a black box.”
The challenge for researchers is to understand their mechanisms of action and to construct them in a coherent manner.
The FDA’s botanical journey dates back to 2003. The agency wrote the first guide in 2004 and revised it in 2016. Since then, the regulator has received hundreds of IND applications and has only received and approved two NDAs.
The FDA regulates plants more as biologics than small molecule drugs, “in that they view plants as complex mixtures,” Cheng said. “For this reason, they treat the whole mixture as the active ingredient. They say very clearly in the guidelines that it is impossible to know all the chemicals in there and that it is not essential to the nature of the active compounds. “
Linking bioassays with clinical parameters is sufficient to meet regulatory needs, as the FDA says it will review “all of the evidence.” The regulator will also take into account historical data for safety purposes, especially for products that have been in use for hundreds of years.