Infinity Pharmaceuticals' (Nasdaq: INFI) top execs sometimes get strange looks when they say they are developing a new drug for pancreatic cancer. This, after all, is a wicked malignancy that usually kills patients in just a few months, and has dashed the hopes of many cancer drug developers over the years.

Yet Cambridge, MA-based Infinity is moving full steam ahead with a new drug candidate for pancreatic cancer, IPI-926, in a mid-stage trial of 120 patients this year. Infinity will offer a clearer picture of why it has moved ahead with this program during a presentation this weekend at the American Society of Clinical Oncology in Chicago. That's where researchers will present data on the first 16 patients with pancreatic cancer who got the Infinity drug in combination with a standard chemo drug.

An interim peek at the data from the first-phase trial showed that three of the first nine patients (33 percent) had their tumors shrink by half or more when they got IPI-926 in combination with standard gemcitabine (Gemzar) chemotherapy. The study was designed to look at safety of a variety of doses, and there was no control group, so it's impossible to say for sure how good that really is compared to anything else. But it was an eye-opening result nonetheless, given that only about 5 percent of patients will typically see that kind of tumor shrinkage when getting the gemcitabine alone, says Julian Adams, president of R&D at Infinity. Common side effects were fatigue, nausea, and an elevation in liver enzymes which can be a sign of liver damage, but which weren't considered serious in this trial, and which were reversible.

"We are circumspect. We don't want to create unbridled enthusiasm. We are humbled by the challenge of this disease," Adams says. That said, he notes that the ongoing mid-stage study of 120 patients is recruiting patients fast, and should be completely enrolled by the end of this year. "The investigator community is jazzed," Adams says.

Pancreatic cancer, once it has spread through the body, usually gives people a life expectancy of just under six months, Adams says. About 36,800 people in the U.S. die each year from pancreatic cancer, according to the American Cancer Society. The really big test for Infinity will be to see if its drug can help those pancreatic cancer patients live longer, which is the main goal of the ongoing trial of 120 patients. Results from that study are expected by late in 2012, Adams says.

Part of what draws attention to the Infinity program is the science. The drug is designed to inhibit a biological pathway known as Hedgehog, which is thought to help tumors grow and thrive when flipped into a mutated form. Infinity scientists showed, in a paper published in Science in 2009, that the drug by itself had no effect on pancreatic cancer in mice, but that it disrupted the dense tissue matrix surrounding tumors, Adams says. By disrupting the tumor's microenvironment, it is thought to help enable cell-killing chemotherapy like gemcitabine to do a better job of penetrating the tumor, Adams says.

The drug helped mice live longer with cancer, but curing cancer in mice isn't the same as curing cancer in people. Seeing tumor shrinkage in three of the first nine patients in a clinical trial does help confirm what Infinity saw in its preclinical studies, but sometimes just because a drug shrinks tumors in the short term doesn't always mean it will prolong lives in the long term.

That's why Infinity has designed the ongoing study of 120 patients so that half will get the usual gemcitabine and a placebo, and the other half will get gemcitabine and IPI-926. The company will compare how long patients live in those two groups. This isn't a squishy, subjective trial endpoint that could lead a drug into a dead end of endless semantic debates about whether a tumor on a CT scan actually shrank or not.

"Overall survival is a hard endpoint. It's the only standard that means anything in pancreatic cancer," Adams says.

Lots of conjectures will be made this weekend over what kind of odds this new Infinity drug has against a very tough opponent in pancreatic cancer. When I pooh-poohed some of the data in my chat with Adams, he acknowledged it's all very early, and that it's a long way away from taking center stage at ASCO, if it ever gets there. His main goal for ASCO this year will be to clearly explain the science to the clinical investigators, who can help make the drug succeed through their enthusiasm for recruiting patients.

So far, so good. But Adams did allow himself the luxury of dreaming just a little bit bigger, about what might happen if the new Infinity drug can help pancreatic cancer patients live even a little bit longer. The drug could then be tested in forms of pancreatic cancer that haven't spread through the body, or in tandem with other forms of chemotherapy. It will probably be another year before Infinity knows for sure whether it has a drug that can be pushed forward aggressively on multiple fronts.

"The good news is investigators are enthused, they love the science, and the explanation here. It really allows us a lot of other avenues for investigation," Adams says.


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Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. Email him at or follow him on Twitter at