Start-up Company Focuses on New Approach to Treating Cancer

When Professor André Lieber first disclosed his novel approach to cancer therapy in 2008, C4C technology manager Angela Loihl immediately recognized it could be “a winner.” Lieber’s team is the only one in the world working to block the action of a key cell surface receptor, CD46, a protein that is active in tumor cells and protects them from being killed by antibodies.

The recombinant protein Lieber has developed reduces levels of CD46 and thus enhances the action of monoclonal antibodies in killing non-Hodgkin lymphoma cells in preclinical studies in vitro and in vivo. Monoclonal antibodies are proteins produced in the laboratory from a type of immune system cell, but used alone they have had limited effectiveness in treating cancer.

Harnessing a Virus
A professor in UW Medical Genetics, Lieber is one of the world’s leading experts on adenoviruses, a family of viruses that commonly cause respiratory illnesses such as colds and bronchitis, but can infect other organs and may not always produce symptoms. Lieber discovered that a rare variant, Adenovirus 35, infected cells by attaching to the cells’ receptors for the CD46 protein. After extensive testing he discovered a mutant, Adenovirus 35 protein with a 20-fold higher affinity for CD46 compared to the native protein. Treating mice with lymphoma with this recombinant viral protein (Ad35K++), followed by the monoclonal antibody Rituxan®, increased their survival compared to using Rituxan with standard anti-CD46 antibodies.

“More than half of non-Hodgkins lymphoma patients treated with Rituxan relapse within a year and become resistant to this drug,” Lieber said. “We think initial treatment with our recombinant protein could significantly improve the effectiveness of Rituxan and also decrease the dosage needed and thus side effects for patients.”

“We’re also excited about this recombinant protein because the manufacturing process is simple and inexpensive, the potential market is large, and so far this approach has limited competition,” C4C’s Loihl said.

C4C Guides Commercialization of Lieber’s Discovery
C4C has filed two provisional patents for Ad35K++ and awarded Lieber a $50,000 Commercialization Gap Fund Grant to continue proof of concept studies. Loihl also helped arrange exclusive licensing to a start-up company called Compliment, a name that is a takeoff on the complement system of proteins whose activation sets in motion production of antibodies to attack cancer cells. Lieber is a founder of Compliment, along with Dr. Darrick Carter, a protein chemist and CEO of Protein Advances, Inc., and Dr. Ron Berenson, a highly regarded oncologist, biotechnology veteran, and until recently CEO of Hemaquest Pharmaceuticals. Now a “virtual company”, Compliment plans to establish research and development operations after funding is secured to begin clinical trials.

Next Big Step: Funding for Clinical Trials
Although Lieber has obtained federal grants and awards totaling around $1 million for his research to date, raising funds for next-stage trials is a huge challenge.

The FDA first requires safety and efficacy trials in non-human primates. These studies will likely begin later this year in partnership with a company that produces monoclonal antibodies.

While Fred Hutchinson Cancer Research Center would like to collaborate on the human clinical trials, the high cost—up to $20 million—is a hurdle. It’s almost impossible to get federal money for these trials, so Lieber and his team must seek funding from the private sector.

“At that point we’ll need major venture capital funding, but it is an attractive investment because there should be a substantial market for our product,” Lieber said. “Monoclonal antibodies are a multibillion dollar business and our therapeutic approach could be applicable for a wide variety of cancers.”

Looking ahead, Lieber is optimistic about bringing his cancer therapy to market with the guidance of the scientific and biotechnology company experts advising his start-up company. He credits Loihl and C4C staff for seeing the potential of his discovery and providing enthusiastic support.

“C4C has been extremely helpful on many levels, from gap funding to prosecution of patent applications, and they were extremely flexible and equitable in out-licensing the patent,” Lieber said. “Everything is moving quickly now, and if all goes well and clinical trials prove safety and effectiveness, this therapy could be on the market within three to five years.”