New immune-boosting drugs like
Earlier this year, Curis partnered with India-based Aurigene to develop several drugs, including one with a similar mechanism of action to Keytruda (pembrolizumab) and Opdivo (nivolumab), which inhibit an immune-restricting “checkpoint” called PD-1. But unlike those medicines, the Curis/Aurigene drug is a small molecule—meaning it could be given in pill form, rather than as an injection or infusion of much larger antibody-based molecules. Fattaey is so optimistic about the technology he told investors during Curis’ second-quarter earnings call in August that the company would rebalance its limited resources to focus largely on the Aurigene collaboration.
“Antibody drugs are being priced at $120,000 to $150,000 a year. Now everyone’s talking about combination treatments, but when you combine two antibodies at $150,000 a year each, that becomes prohibitive,” Fattaey says. “We may have the opportunity to send patients home with a bottle of pills.”
The effort to pack complex drugs into pill form has long been a holy grail in biotech. Traditional biotech manufacturing is a laborious—and by extension, expensive—process that requires growing proteins in live organisms like hamster ovary cells. Curis is so optimistic about Aurigene’s technology for packaging antibodies in pill form that it vowed to pay $52.5 million for each of the first two programs under the collaboration, in return for worldwide collaboration rights (excluding Russia and India). Curis expects to begin clinical development of the immuno-oncology drug, which targets a relative of PD-1 called PD-L1, by the end of the year.
The scientists from Curis and Aurigene are far from the only ones looking to improve upon drugs like Keytruda and Opdivo. At the inaugural International Cancer Immunotherapy Conference, which began September 16 in New York, for example, scientists from Stanford University School of Medicine unveiled a small protein they’re working on that targets PD-L1 and that seems to produce more anti-tumor activity than traditional antibodies. A company called NewLink Genetics is working on a small-molecule inhibitor of another immune checkpoint called IDO.
Small molecule drugs could prove even more valuable as combination immuno-oncology treatments start to take hold, Fattaey contends. Although Curis has yet to announce its targets for its experimental drug, inhibiting PD-L1 has proven a particularly promising approach in lung cancer, bladder cancer and Hodgkin’s lymphoma, he says. Several companies have already partnered on checkpoint-inhibitor combination trials in various tumor types, and Curis hopes to someday be part of that effort to unleash the immune system from multiple different angles. “As we begin to examine and explore combination treatment strategies, our hope we could do all-oral combinations, rather than the patients having to continue to come in for injections,” Fattaey says.
Curis’ efforts come amidst a broad push to lower the cost of cancer drugs. All of the new cancer drugs approved in 2014 cost $120,000 a year or more, according to an editorial authored by 100 angry oncologists in last month’s edition of the Mayo Clinic Proceedings. Even when those drugs are covered by insurance, out-of-pocket expenses for the average patient can be as high as $30,000 a year, they noted. “Patients with cancer then have to make difficult choices between spending their incomes (and liquidating assets) on potentially lifesaving therapies or foregoing treatment to provide for family necessities (food, housing, education),” the authors wrote.
And convincing payers around the world to cover cutting-edge cancer drugs remains a challenge. Earlier this month, Merck won approval from the National Institute for Health and Care Excellence (NICE)—the U.K.’s drug-cost watchdog—for Keytruda to be covered by the National Health Service (NHS) to treat some types of advanced melanoma. The company is granting NHS a discount, however, according to a Reuters report.
Curis is embarking on its attempt to pioneer a more affordable generation of cancer immunotherapy with seriously limited resources. Most of the company’s revenues come from royalties on Erivedge (vismodegib), a drug to treat basal cell carcinoma that it licensed to Roche’s Genentech unit. Curis’ royalty revenues rose 19% year-over-year to $3.7 million in the first six months of 2015, but the company had a net loss of nearly $40 million. Its share price has dropped 22% in the last three months to $2.50.
Undeterred, Fattaey and his team of scientists continue to preach the value of their gameplan to both the medical and financial communities, appearing at two oncology conferences and three investment conferences this summer alone. “We see an oral checkpoint inhibitor as a tool in the armament for physicians to design a treatment strategy for each patient,” he says. “And we certainly see small molecules as consistent with the future of payment strategies.”
