Norwegian biotech Clavis Pharma and privately held Clovis Oncology signed an agreement for the development and commercialization of Clavis’ CP-4126 anti-cancer compound, currently in a mid-stage trial as a treatment for pancreatic cancer. Clovis Oncology is a relatively new company led by former Pharmion executives who had raised $145 million in venture capital in the spring of this year with the idea of finding promising oncology programs to develop. Now they have their deal, which includes a $15 million signing fee for Clavis, up to $365 million in milestone payments, and tiered double-digit royalties on sales.

 

Under the terms of the agreement, Clovis Oncology will assume full responsibility for the clinical development of CP-4126 and will commercialize the compound in the United States, Europe, Canada, and Central and South America. Clavis Pharma will retain an option to co-promote and share profits in Europe. The companies will also collaborate on the development of a companion diagnostic to identify patients most likely to benefit from the treatment.

 

“We view this agreement as an important validation of Clavis Pharma's potential to generate multiple novel cancer drugs with enhanced performance over existing therapeutics,” says Geir Christian Melen, CEO of Clavis Pharma.

The design of the ongoing phase 2 study in pancreatic cancer will also be amended to enroll approximately 250 patients in an international, randomized, comparative trial of CP-4126 versus gemcitabine (Eli Lilly’s Gemzar) with overall survival as a primary endpoint. CP-4126 is a novel, lipid-conjugated form of gemcitabine generated using Clavis’ proprietary Lipid Vector Technology and designed to improve treatment the therapeutic profile of outcomes in patients with pancreatic and certain other solid tumors.
 

CP-4126 was generated using Clavis Pharma's proprietary Lipid Vector Technology and has been designed to improve the therapeutic profile of gemcitabine, the current standard treatment for advanced pancreatic cancer, so that it can enter cancer cells without requiring uptake by a specific transporter molecule. It is estimated that pancreatic tumors in up to two-thirds of patients have limited cellular uptake of gemcitabine due to deficient expression of the transport protein, hENT1 on the tumor cell surface. A number of independent studies have shown a correlation with low levels of hENT1 and poor outcomes after gemcitabine therapy. Published research has also suggested that hENT1 levels predict outcome in lung cancer patients treated with gemcitabine-containing chemotherapy. 

“Gemcitabine is the standard of care in pancreatic cancer, but accumulating data suggest that a significant percentage of patients may derive little benefit from its use because of low expression of the hENT1 transporter that allows gemcitabine to enter tumor cells. In vitro data demonstrate that CP-4126 overcomes this resistance mechanism,” says Patrick Mahaffy, president and CEO of Clovis Oncology. “We now have the opportunity to show that a cytotoxic, which remains the backbone of cancer therapy, can become an effective, targeted therapy in this large subset of patients. Our development philosophy is to focus on providing meaningful benefit to subset patient populations with unmet medical need and we believe CP-4126 will do exactly that."   

 

Due to its different molecular design, CP-4126 is absorbed by cancer cells independent of hENT1 levels, raising the prospect of a major improvement in drug efficacy in the significant and potentially poorly-served group of hENT1-low patients. 

Expression of hENT1 in tumor tissue will be measured during the trial and patients categorized into hENT1-high or hENT1-low groups prior to final analysis, with primary emphasis on comparative overall survival in the hENT1-low population. Data from this trial are expected in the first half of 2012. As a key element of the clinical program, the companies will develop a validated companion molecular diagnostic test to reliably determine pancreatic tumor hENT1 expression and enable patient stratification.

 

“Confirmation of the hENT1 hypothesis offers a promising and novel enhancement to current treatments for patients with pancreatic cancer,” says Daniel Von Hoff, physician in chief, Translational Genomics Research Institute and  clinical professor of medicine at the University of Arizona. “This is an exciting new concept that may enable both superior targeting of an established drug, gemcitabine, as well as providing a new, rational treatment option, CP-4126, to hENT1-low patients.”

 

CP-4126 has been granted orphan drug status for the treatment of pancreatic cancer in the European Union and is currently being considered for a similar designation by the FDA in the US. If, as hypothesized, the new compound works better than Gemzar, it could potentially achieve blockbuster status. Gemzar and had sales of $1.72 billion in 2008.