About Us
BrYet is a privately-owned biotech company focused on the discovery and development of novel physics-based, first-in-class therapies for metastatic liver and lung cancers. BrYet’s discovery program of injectable nanoparticle generators has yielded a lead drug candidate, ML-016, which will be studied in humans in a Phase I clinical trial and has the potential to treat a broad range of patients with hard to treat cancers.
About Lung and Liver Malignancies
The leading cause of cancer deaths are lung and liver malignancies. These include primary tumors that originate locally and metastases which originate elsewhere and then spread to these organs (secondary).
Lung cancer is the most common cancer worldwide, accounting for 2.1 million new cases and 1.8 million deaths in 2018. The prognosis for patients suffering from lung cancer is very poor, with >50% of patients dying within 1 year of being diagnosed. Similarly, liver cancer is one of the most prevalent types of cancer and is the 9th leading cause of cancer deaths. According to the NCI, 41,000 patients in the US were diagnosed in 2017 and 28,000 patients died in the same year. Owing to the aggressive nature of liver cancer (hepato-biliary carcinoma), the survival rates are very poor, with 44% of patients diagnosed at an early stage having a 5-year survival rate of only 31%. For those whose liver cancer has spread to surrounding tissues, organs or lymph nodes, this dramatically reduces to a 5-year survival rate of 11%. The survival rates of liver cancer are further aggravated by other medical conditions which are increasing (e.g. Hep B & C virus, Type 2 diabetes, obesity, liver cirrhosis, tobacco and alcohol).
Lung and liver are cited to be the most common sites of metastases, with lung metastases identified in 30-55% of all cancer patients (dependent on the type of primary cancer). Metastatic tumors in the liver are 20 times more common than primary tumors.
Our Technology
An introduction to ML-016 (iNPG-pDox)
The problem
Only a small fraction of administered cancer drugs accumulate in tumor cells, drastically limiting efficacy. At the same time, cancer drugs can damage healthy cells, causing severe side effects.
The lead product ML-016 (iNPG-pDox): what is it?
The product is an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. This iNPG is a particle that can be loaded with chemotherapeutics. It is built by conjugating doxorubicin to a polymer backbone by means of a pH-sensitive linker and loading the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. The result is a four-component new chemical entity, specifically designed to overcome biological barriers and eliminate adverse side effects.
How it works
Once released from iNPG, pDox spontaneously forms particles in aqueous solution
Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics. It then releases pDox nanoparticles that are internalized by tumor cells
Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps.
Results - Therapeutic efficacy
The lead product represents a unique solution, as iNPG-pDox achieved functional cures in 40–50% of treated mice with metastatic breast cancer.
Overcoming obstacles in drug delivery
By partitioning biological barriers encountered by cancer therapeutics en route to tumors into distinct tasks, we have developed a construct capable of successively overcoming these obstacles. This includes selective bio-barrier penetration and specific actions against therapy-resistant cancer cells.
Drug transportation to the right regions
We have demonstrated natural tropism of the therapeutic carriers to lungs and liver (which are preferential organs of metastasis). This was achieved through rational design with regards to carrier size and geometry.
Drug concentration remains high over time
Once localized, high concentrations of Dox were maintained in these organs for over 1 week after administration, with the particles effectively serving as long-term nanotherapeutic-generating vascular depots (i.e. releasing the drug over time).
Effective attack of cancer stem cells
The pDox molecules were shown to self-assemble in situ into nanoparticles, which could in turn leak into the tumor interspace. pDox nanoparticles were then internalized into tumor cells (by endocytotic pathways), followed by transport to the perinuclear region and pH-sensitive separation of Dox from pDox. This enabled the release of Dox far from the sequestering effects of efflux pumps and overcoming of cell membrane-based MDR mechanisms
Scientific Advisory Board
Professor Mauro Ferrari (Chair)
Professor Mauro Ferrari (Chair)
Professor Mauro Ferrari (Chair)
Professor Mauro Ferrari is an academic entrepreneur, Board member of Arrowhead Pharma since 2009, and the pioneer of iNPG, transport oncophysics, nanomedicine, bioMEMS, and multi-stage vector therapeutics. In his academic career he has over 500 archival publications, has received numerous honours and awards, has been elected to national a
Professor Mauro Ferrari is an academic entrepreneur, Board member of Arrowhead Pharma since 2009, and the pioneer of iNPG, transport oncophysics, nanomedicine, bioMEMS, and multi-stage vector therapeutics. In his academic career he has over 500 archival publications, has received numerous honours and awards, has been elected to national and international academies, and has over 50 issued patents in the US and worldwide.
He served as a tenured professor and academic executive at the University of California Berkeley, the Ohio State University, the University of Texas MD Anderson Cancer Center and Medical School Houston, the National Cancer Institute, Houston Methodist and Well Cornell Medical College, the University of St Thomas, and is currently serving on the faculty of the University of Washington.
Previously, he was President and CEO of Houston Methodist Research Institute, and EVP of Houston Methodist Hospital System.
Professor Ferrari trained in Mathematics (Italy); Mechanical Engineering (Berkeley); Medicine (Ohio State, no degree); Business (Harvard & Penn, no degree).
Dr Andrew von Eschenbach
Professor Mauro Ferrari (Chair)
Professor Mauro Ferrari (Chair)
Dr Andrew von Eschenbach was the Commissioner of the United States Food and Drug Administration from 2006–2009. He became acting Commissioner in September 2005 and was confirmed as Commissioner by the Senate in December 2006. He was previously the 12th director of the National Cancer Institute.
Previously, Dr von Eschenbach held several po
Dr Andrew von Eschenbach was the Commissioner of the United States Food and Drug Administration from 2006–2009. He became acting Commissioner in September 2005 and was confirmed as Commissioner by the Senate in December 2006. He was previously the 12th director of the National Cancer Institute.
Previously, Dr von Eschenbach held several positions with The University of Texas M. D. Anderson Cancer Center, beginning as a urologic oncology fellow, and later becoming chair of the department of urology. He was founding director of the Prostate Cancer Research Program, director of the Genitourinary Cancer Center, and held the Roy M. and Phyllis Gough Huffington Clinical Research Distinguished Chair in Urologic Oncology.
Dr von Eschenbach currently serves on the board of directors of BioTime and Viamet Pharmaceuticals. He also runs his own consulting company, Samaritan Health Initiatives.