In early 2002, the Finnish-born scientist Erkki Ruoslahti stepped down as CEO of what is now San Diego’s Sanford Burnham Prebys Medical Discovery Institute. He moved to Santa Barbara, CA, where he established what he calls “a little subsidiary” of the SBP institute, and joined the faculty of UC Santa Barbara. He continued his research on tumor vasculature and cancer metastasis.
Now 77, Ruoslahti (pictured above) is back in San Diego as a founder and CEO of DrugCendR, a startup developing new ways to improve the uptake of anti-cancer drugs in solid tumors. The company spun out of the SBP institute in 2015 with technology developed in Ruoslahti’s lab by DrugCendR co-founders Kazuki Sugahara and Tambet Teesalu.
The three founders provided close to $1 million of their own money to get the company started, Ruoslahti said yesterday. That should be enough for DrugCendR to complete the last phase of pre-clinical studies now underway at contract research labs in the United States and China.
“We expect to put together our IND application by the end of this year,” Ruoslahti said, referring to an investigational new drug application and the formal process for seeking FDA approval for marketing a new drug in the United States. “We wanted first to build value and make sure the project is well on its way before we turn it over to someone else.”
Today, DrugCendR is announcing that it also has entered into a partnership with a Chinese company, Xiamen Tobefar Technology, to develop its lead product candidate for the Chinese market. Xiamen, which is partly owned by Peking University and an investor, the Beijing Institute of Collaborative Innovation, also plans to develop a diagnostic assay to identify the tumors that are most likely to respond to the treatment.
DrugCendR’s lead product candidate is a tumor-penetrating peptide known as integrine-binding arginine-glycine-aspartic acid, or iRGD, which increases the uptake of anti-cancer drugs by activating a transport pathway found only on the blood vessels closely connected to solid tumors.
Through the years, Ruoslahti said “We developed a lot of peptides that seek out tumor vasculature. In Santa Barbara, we started finding peptides that not only found the vasculature but actually penetrated and spread out throughout the tumor.”
The iRGD peptide helps to slow cancer from spreading, but Ruoslahti said it mostly increases the permeability of tumor cells, opening the way for more potent anti-cancer drugs to penetrate a tumor. The iRGD peptide does not have to be coupled with an anti-cancer molecule to work, Ruoslahti said. So it could be used with an existing anti-cancer drug already approved by the FDA.
“One of the reasons chemotherapy and just about any other cancer therapy fails to work is that the drugs don’t reach all of the tumor cells,” Ruoslahti said. Tumors typically are protected by thick connective tissues that grow around them, he explained. The internal pressure of tumor cells also is higher than normal cells, which can make it hard to get anti-cancer drugs into tumor cells, Ruoslahti said.
The iRGD peptide skirts the fibrotic tissue surrounding a tumor by initially targeting a receptor that is overly expressed on blood vessels that are feeding a tumor, Ruoslahti said. Once inside, the iRGD peptide targets a different receptor that activates the pathway in tumors but not in healthy tissue. The internal pressure of tumor cells also is less of a factor because the transport pathway opened by iRGD, known as the CendR pathway, actively conveys molecules into tumor cells. “The important thing is that it is an active transport pathway,” he said.
DrugCendR’s approach appears to work with any solid tumors, Ruoslahti said, but the company is focusing initially on pancreatic cancer.