For most Big Pharma companies, the annual meeting of the American Society of Clinical Oncology (ASCO) is one of dozens of important venues for spotlighting data on experimental drugs. But for tiny Cyclacel Pharmaceuticals (NASDAQ: CYCC)—which is focused on developing cancer treatments—the confab of oncologists, cancer researchers, and drugmakers is the make-or-break event of the year. “We live and die by the ASCO timetable,” says Spiro Rombotis, CEO of Cyclacel, which is based in Berkeley Heights, NJ.
That timetable reached a key point on May 19, when ASCO released the abstract for Cyclacel’s poster presentation of a pivotal trial of sapacitabine, its oral drug to treat acute myeloid leukemia (AML), a deadly form of blood cancer. On June 6 at the ASCO conference in Chicago, Cyclacel will present detailed data from the trial, in which its drug is being tested in combination with an existing product called decitabine (Dacogen), developed by Eisai.
Some on Wall Street are clearly expecting good news. Roth Capital Partners analyst Joseph Pantginis wrote in a May 19 report that he was “encouraged by this first look into the combination of the two drugs.” He has a “buy” on Cyclacel’s stock and a 12-month price target of $7. The company’s shares closed at $1.63 on May 27.
The journey to Phase 3 for sapacitabine has been a long one for Cyclacel. The company was founded in the UK in 1996 by David Lane, a professor at the University of Dundee who discovered that a protein called p53 is a key player in tumor suppression. “He showed you could induce lethality in cancer cells that were resistant to other therapies,” Rombotis says.
Cyclacel was founded on the hope of developing compounds that could control “cell cycle regulation”—essentially by inducing cancer cells to commit suicide, while sparing the normal cells around them. Cyclacel raised more than $50 million in private financings, which was enough to support 85 employees and five drug-development programs, Spiro says.
The company went public in 2006, moved its headquarters to New Jersey—and promptly ran headfirst into one of the worst market downturns in history. Desperate to reduce its cash burn, Cyclacel’s management team shrunk its staff to 21, and pared down its drug-development efforts to focus on the most promising programs. The company now has three compounds in clinical trials.
Sapacitabine is the most advanced of those compounds. The drug, called a “nucleoside analog,” works by interfering with DNA synthesis in cancer cells. That, in turn, induces the arresting of the cells’ division cycle. Unlike the most commonly used chemotherapy treatments for AML, which are infusions that have to be given in medical clinics, sapacitabine is a pill that patients can take at home. There have been side effects in trials, such as nausea, but the drug has been tolerable enough for some patients to take it for 12 cycles—as opposed to just two cycles with standard chemotherapy, Rombotis says.
AML is a rare disease, but a potentially lucrative market opportunity. The disease strikes about 13,000 patients a year, most of them elderly. The most commonly used treatment is a chemotherapy regimen that is too toxic for many older adults to handle. Most patients die within a year of diagnosis, Rombotis says, which is why so many oncologists have been angling to get their sickest patients into trials of sapacitabine. “If we shift the natural progression of the disease, this will be a blockbuster,” he predicts.
Cyclacel hasn’t discussed the pricing of its drug or predicted the overall size of the market. But Genzyme once predicted the AML market to be $600 million a year—a reasonable estimate, Rombotis says, when you consider that similar treatments are priced around $50,000 per treatment cycle. Cyclacel is also developing sapacitabine for myelodysplastic syndromes (MDS) and lung cancer—both of which are even bigger market opportunities than AML, Rombotis says.
The first hint of what Cyclacel’s drug might achieve in AML will emerge at ASCO. Physicians and analysts alike will be looking carefully at the 30-day and 60-day mortality data. In AML, Rombotis says, 30-day mortality rates of 10 percent or less are considered okay. Anything between 10 and 20 percent is worrisome, and 20 percent or more is a “no go,” he says. “At 60 days, we look at mortality as an indicator of efficacy,” Rombotis adds. “If you don’t start to move the curve at 60 days, you’re not going to get there.”
Drug cocktails to fight cancer have become popular over the past decade, so Rombotis hopes that combining sapacitabine with decitabine will produce a more potent—but more tolerable—treatment than the standard chemotherapy regimens. Unlike other cocktails, in which several treatments are given simultaneously, Cyclacel’s treatment regimen consists of alternating one-month therapies: decitabine infusions, then sapacitabine pills that the patients take at home, then decitabine, and so on.
It will take several more years for Cyclacel to prove definitively that its treatment can make enough of a difference in AML to win over the FDA. But Rombotis and his colleagues are inspired by patients in their trials that have achieved seemingly impossible recoveries. During a meeting at Cyclacel’s headquarters, Rombotis brought along the company’s 2008 annual report, which featured Marvin Arnold, a Texan who participated in an early trial of sapacitabine. He was 81 years old when he was diagnosed with AML and placed in the trial. “This man had two more birthdays,” Rombotis says, holding up the annual report that pictures Arnold on the cover.
Rombotis knows Cyclacel will ultimately have to prove that its treatment improves survival by at least three months on average. “Ideally, we want to push survival out beyond six months,” he says. “Otherwise we’re not going to make a dent in this disease.”