Promising anti-cancer immunotherapy technologies developed by a pair of star researchers at the University of Minnesota have been licensed and put on a fast track to commercialization by a veteran biotech entrepreneur.

Oxis International (OTCQB: OXIS), and its wholly owned subsidiary Oxis Biotech Inc., are based in Tampa, Florida and led by Anthony Cataldo, whose long entrepreneurial history spans several different industries. Before assuming the helm of Oxis in 2014, his most notable biotech achievement was building Lion Biotechnologies (Nasdaq: LBIO) into a $500 million market-cap company through the development of licensed immunotherapies targeting metastatic melanoma.
 
His latest venture is to commercialize two key cancer immunotherapy licenses obtained from U of M researchers. They were developed by Daniel Vallera, a professor of therapeutic radiology, and Dr. Jeff Miller, deputy director of the U’s Masonic Cancer Center. Both use novel drugs to specifically target cancer cells with killer payloads while leaving healthy cells unharmed, thus avoiding the toxic side effects of radiation therapies.
 
Of the two, the furthest along is a drug called OXS-1550, which OXIS licensed personally from Vallera last year. It targets B-cell lymphoma—a type of cancer that forms in the immune system cells known as B-cells. Most B-cell lymphomas are non-Hodgkin lymphomas, of which there are many different types, such as Burkitt lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). As the most common type of non-Hodgkin lymphoma among adults, it has an annual incidence of 7-to-8 cases per 100,000 people per year.
 
Vallera’s drug candidate is comprised of antibodies that seek out proteins present on the surfaces of most B-cell lymphoma and leukemia cells and delivers a payload of diphtheria toxin. When OXS-1550 binds to the cancer cells, they internalize the drug and are killed due to the action of the toxic payload. 
 
After the drug demonstrated success in a Phase 1 human clinical trial with B-cell lymphoma/leukemia patients, Oxis launched a Phase 1/Phase 2 trial earlier this year at the Masonic Cancer Center in Minneapolis.  The company reports some 32 patients have participated so far.
 
Under the agreement, Vallera is to receive an upfront license fee, royalty fees, and certain milestone payments. He was named to the company’s scientific board in June, saying in a statement, “We believe OXS-1550 to be a powerful alternative to existing chemotherapies, since many patients fail chemotherapy or reach the toxic limits of their therapy.”
 
Oxis, meanwhile, broadened its relationship with the U of M cancer researchers this summer with the licensing of another cutting-edge immunotherapy targeting leukemia. This one, co-developed by Vallera and Miller, was obtained from the University itself and is being touted as opening a new front in the science of stimulating the body’s own immune system to attack cancer cells.
 
Dubbed Trispecific Killer Engager, Oxis and its inventors are hailing it as a breakthrough technology that takes an existing method to kill cancer cells—the “bispecific” killer engager or BiKE—and adds a third element that also stimulates a confined, local production of the patient’s own NK immune cells. The result, they say, is a “tri-specific” killer engager, or TriKE, that greatly enhances the cancer-killing effect with minimal side effects.
 
Oxis’ Cataldo is proposing TriKE as a cheaper and safer alternative to bi-specific CAR T-cell therapy, “which is known to be expensive and has been shown to carry significant side effects.”
 
“The bi-specific antibody platform is well known for its ability to kill cancer cells via antibody dependent cell-mediated toxicity,” he said in a released statement. “However, current successes in immunotherapy indicate that enhanced killing will not be enough. We believe the TriKE platform from University of Minnesota has found a way to expand the immune cell population within the patient, but not at the expense of creating a toxic environment.”
 
Dr. Miller added, “The TriKE platform we have licensed to Oxis is designed to address the issue of making NK cells antigen specific by modifying a bi-specific antibody platform and adding a third signal by inserting a modified IL-15 cross linker. IL-15 is known as a chief activator of NK cells that can enhance an anti-cancer immune response.”
 
This platform is unique, he said, “because it simultaneously delivers a priming, expansion, killing, and activating signal directly to the immune cell as it is in contact with the cancer cell. We believe that TriKE can mediate specificity and deliver an immune expansion signal locally (instead of systemically) which has the potential to diminish toxicity.”
 
The U of M researchers said they are working with Oxis to initiate FDA-approved clinical trials for TriKE after encouraging pre-clinical results.