TEL AVIV, Israel—RedHill Biopharma Ltd., an Israeli biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally administered, small-molecule drugs for inflammatory and gastrointestinal diseases, including cancer, is collaborating on research with Leipzig-based Fraunhofer Institute for Cell Therapy and Immunology (IZI), for the evaluation of RedHill’s Phase 2-stage oncology drug candidate, RP101. IZI is a research unit of the Fraunhofer Society.
The research collaboration will involve testing RP101 in preclinical oncology models, including pancreatic cancer, in combination with standard-of-care chemotherapies to support existing Phase 1 and Phase 2 clinical data.
“We are excited to be collaborating with one of the largest and most prominent applied research organizations in the world,” said Adi Frish, RedHill’s senior vice president of business development and licensing. IZI investigates and develops specific problem solutions at the interfaces of medicine, life sciences and engineering. The Institute practices contract research for biotechnological, pharmaceutical and medical-technological companies, hospitals, diagnostic laboratories and research facilities. The collaboration could mean a breakthrough in one of the deadliest forms of cancer.
RedHill acquired an exclusive option to purchase RP101 and next-generation compounds from RESprotect GmbH in 2014. RP101, a proprietary, first-in-class, heat shock protein 27 (Hsp27) inhibitor, administered orally, may prevent the induction of chemoresistance and thus maintain the sensitivity of tumors to chemotherapy and potentially increase patient survival. These properties could be significant in the treatment of pancreatic cancer.
Pancreatic cancer is especially deadly, because it is difficult to detect, quick to progress and resistant to chemotherapy. Thus, as Shani Maurice, business development manager of RedHill Biopharma, explained, “Pancreatic cancer is characterized as a disease with some of the highest unmet need in oncology, with overall five-year survival of approximately 5 percent. The prognosis of the disease is linked to the stage of the tumor at the time of diagnosis, which often occurs after the tumor has reached an advanced stage. Surgical resection is the only curative treatment, but less than 20 percent of patients with pancreatic tumors are eligible for surgical resection.”
RP101 is based on a new mechanism of action of the antiviral drug brivudne, a nucleoside analogue approved in several European countries for the treatment of herpes. Granted Orphan Drug designation for the adjunct treatment of pancreatic cancer in both the United States and Europe, RP101 completed several Phase 1 and Phase 2 studies with a total of 249 subjects. The studies determined that pancreatic cancer patients co-treated with RP101 and one or more chemotherapy agents had longer overall survival than control pancreatic cancer patients treated with chemotherapy alone. In a randomized, placebo-controlled Phase 2 pancreatic cancer study, median overall survival was longer in patients receiving chemotherapy and RP101 than in those receiving chemotherapy and placebo in a subset of patients with high body surface area in the United States.
According to Maurice, RP101 binds to Hsp27, a chaperone protein which is found in abnormally high levels in cancer cells, and inhibits its activity. The overexpression of Hsp27, which results in the amplification of a multidrug-resistance (MDR) gene, has been linked to tumor resistance to cytotoxic drugs and the development of metastasis. Chemoresistance limits the effectiveness of chemotherapy and can ultimately lead to treatment failure. By inhibiting Hsp27, RP101 may prevent chemoresistance and enhance the sensitivity of tumors to chemotherapy. Gemcitabine, the standard of care for patients with advanced, unresectable pancreatic cancer, works by inhibiting cellular DNA synthesis and arresting tumor growth. Thus, they work via different mechanisms of action.
“As part of the collaboration between the two companies, Fraunhofer provides the experience, knowledge and skills required to conduct the preclinical research with RP101 that RedHill is sponsoring,” Maurice explained. Fraunhofer IZI is conducting real-time monitoring of tumor engraftment, tumoricidal efficacy and response to treatment with RP101 in combination with standard-of-care chemotherapies.
Results from the studies are expected during the first half of 2016, she said. RP101 is currently in preclinical studies, and much of its future clinical development plans will be based on the results of these studies.
Maurice concluded, “Pancreatic cancer is the fourth-leading cause of mortality in western countries. With 338,000 new cases diagnosed in 2012, pancreatic cancer is the 12th most common cancer in the world. According to GlobalData, the total worldwide sales of pancreatic cancer therapies are estimated to reach approximately $1.6 billion by 2017.”