Merrimack Pharmaceuticals (MACK) has taken its share of punches from investors over the past year while trying to prove that its computer-aided drug discovery approach can lead to effective therapeutics. But the Cambridge, MA-based company can finally talk about some good clinical news today, because it might have a shot to break into the notoriously tough field of pancreatic cancer.

Merrimack today is releasing the top-line results from a 417-patient late-stage study of MM-398, a nanotherapeutic derivative of the old chemotherapy drug irinotecan. The results are mixed, but ultimately positive for Merrimack. On one hand, MM-398 met its study goal. When taken in combination with chemotherapy drugs 5-flourouracil (5-FU) and leucovorin, it helped pancreatic cancer patients who hadn't responded to prior therapies—very sick patients—live some 1.9 months longer than patients who got only 5-FU and leucovorin. Merrimack also said the drug, in combination with 5-FU and leucovorin, helped slow the progression of patients' tumors in a statistically significant way, though it didn't provide any specific details. Merrimack will present more data from the study at a medical meeting in June, according to CEO Bob Mulroy.

On the other hand, MM-398 failed to produce similar results when given to patients on its own, and led to more side effects. Patients on MM-398 alone lived a median of 4.9 months, compared to 4.2 months for those on chemo alone.

"The trial was set up to test two different regimens, and we were trying to thread a needle of finding a regimen that was tolerable in a very sick patient population, and be [strong] enough to have activity on the tumor," Mulroy says. "And what we saw was there was evidence of activity with the monotherapy—and we will look at the data and examine it—but we were able to thread that needle with tolerability of the [combination] regimen as well as [get] good solid activity on the tumor."

This is important for Merrimack, because it's the first time one of its nanoparticle chemo drugs—which are essentially supposed to hit tumors more specifically, and for longer, than regular chemotherapies—have provided a clinically meaningful benefit in a large trial. MM-398 is designed to use tiny lipid nanoparticles to ferry the chemo drug irinotecan to hard-to-reach pancreatic cancer tumors, for instance, by piggybacking on the body's own immune cells.

[Updated with stock price] Shares of Merrimack soared about 70 percent, to $7.15 apiece, in pre-market trading early Thursday.

The most common side effects attributed to MM-398 were diarrhea, vomiting, and neutropenia, a depletion of infection-fighting white blood cells. But Merrimack also noted that 2 percent more of the patients on the MM-398 combination regimen suffered sepsis—a potentially fatal bloodstream infection—than those given chemotherapy alone.

"The top line safety data we were very pleased with, particularly relative to this cancer patient population," Mulroy says.

Indeed, Merrimack believes the data are good enough to submit a new drug application with the FDA, particularly given how few effective options there are for pancreatic cancer patients, and how tough it is to show a benefit. Pancreatic cancer is extremely fast-moving—by the time it is detected, the cancer typically can't be surgically removed, and patients usually die within months. As such, it's the fourth-leading cause of cancer death in the U.S., despite the fact that it accounts for just over 2 percent of the cancers diagnosed annually. About 46,000 people in the U.S. are diagnosed with pancreatic cancer every year, and around 40,000 of them die, according to the American Cancer Society.

Front-line treatment options for pancreatic cancer are mostly built around the chemo drug gemcitabine. Celgene, for example, won FDA approval late last year to begin selling protein-bound paclitaxel (Abraxane) in combination with gemcitabine as a first-line pancreatic cancer regimen after it extended patients' lives in a study by an average of 1.8 months. But Mulroy notes that there's little alternative to such regimens for people who don't respond—all of the pancreatic cancer drugs approved over the past 25 years are part of front-line treatments. Yet about half the patients diagnosed are eligible to move on to some sort of second-line therapies, Mulroy says.

"We have the first drug to show a survival benefit for patients who are refractory to front-line gemcitabine-based therapies," he says. "We're hopeful that we can be a great option for those patients now."

The company plans to file an NDA with the FDA "as soon as possible," seeking approval of a regimen of MM-398 in tandem with the two chemo drugs, according to Mulroy. The FDA granted Merrimack an orphan drug designation for MM-398, giving it longer market exclusivity.

Mulroy also believes the trial shows that the company's approach for making nanotherapeutics out of chemotherapy drugs can produce a benefit. He says that MM-398, for instance, was specifically designed to try to go after very tough-to-treat tumors with poor blood supply, which are harder to treat with drugs injected into the bloodstream. MM-398 is supposed to avoid this delivery problem and accumulate around these tumors by targeting macrophages, immune cells that surround pancreatic cancer tumors. The idea is that the macrophages would potentially help deliver, rather than block, the nanoparticle chemo drug, and the drug's toxic effects would last longer. Mulroy says that seeing MM-398 benefit a patient group that has seen "really no benefit from most therapies for awhile" has given the company more confidence to think about it as a potential first-line treatment for pancreatic cancer, or a possible drug in other cancer types. The company is testing MM-398 in lung and brain cancer as well, for instance.

This is the type of benefit Merrimack is hoping to show by making nanotherapeutics out of other chemotherapy drugs, like doxorubicin. It's also the type of news the company hasn't been able to give to investors yet. The company, founded by scientists at Harvard University and MIT, is based on a drug discovery approach leaning heavily on computer models and companion diagnostics, trying to accurately predict who should take its drug candidates, and who shouldn't, with the idea of designing cheap, efficient late-stage trials. Another cancer drug, MM-121, for instance, is in a number of mid-stage trials that Merrimack has said are designed to find the right subgroups of people for a prospective Phase 3.

Still, those studies haven't yet produced statistically positive results, leading to a few investor sell-offs, and not much upside in Merrimack's stock since the companywent public in early 2012. That's why Mulroy is touting today's data as so important to Merrimack's future.

"We view this as a proof of concept for the technology as it was engineered," he says.

This article originally appeared on Xconomy, along with: