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'Ruble' Slippers: Russian Cash in Argos' $42M Phase III Raise

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By Randy Osborne
Staff Writer

Argos Therapeutics Inc.’s Series E financing – which has raised $42.5 million so far, including $30 million from the venture arm of a Russian pharma firm – is staying open and could turn into enough for the company to finish its pivotal Phase III trial with AGS-003, a personalized immunotherapy for metastatic kidney cancer.

“I think we’ve got a good shot at it,” said Jeff Abbey, president and CEO of Durham, N.C.-based Argos. “This gets us into 2015, so we’re about a year short of finishing [the Phase III trial],” which is expected to last until the end of 2015 or the start of 2016. Other investors are showing interest, and “the sum total would get us at or higher than $60 million, if they all come through,” and that is the amount required to reach data points, he told BioWorld Today.

Pharmstandard International SA, the venture arm of Moscow-based Pharmstandard, made the investment, and the drug development firm separately negotiated a license that provides rights to Argos’ Arcelis platform, starting with AGS-003, and including options to commercialize other programs as well in the Russian Federation and Commonwealth of Independent States.

It’s the first time Pharmstandard has invested in the U.S., though the firm “did a separate deal with a cell therapy company in a completely different, unrelated area, in Germany, in 2012,” so Argos’ general approach “they knew something about, at least in terms of cell therapy manufacturing,” Abbey said.

Korean investor Green Cross Corp. is also part of the round. “They actually have a T-cell-based immunotherapy program that they’re developing in South Korea in the clinic already,” Abbey said. Talks with Green Cross began at the J.P. Morgan Healthcare Conference in San Francisco in January, “and quickly became formalized as the term sheet came together with Pharmstandard. I thought the same approach could work with Green Cross, and sure enough, it was exactly what they were interested in doing,” though the terms of the license are “slightly different,” he said.

Argos’ Arcelis platform involves two steps. “The first thing that happens is that you need a vehicle to deliver the antigens,” Abbey said. “That’s the cellular part of what we do, and for that we take a leukopheresis from patients. Those are shipped to our centralized manufacturing facility, and we make dendritic cells [that are] highly optimized, fully functional in a cancer or HIV patient who has an immune system that is severely compromised.”

The second part involves a small piece of the patient’s tumor or diseased tissue. “In the case of kidney cancer, this is quite easy, because these patients get surgery,” Abbey said. “It gets shipped to us in a kit at room temperature. We take the messenger RNA from the tumor cells, and use a polymerase chain reaction process to make as many copies of that RNA as we could ever possibly use.”

Next, the RNA is loaded into the dendritic cells. “You then get these fully optimized dendritic cells which are expressing all of the antigens on its cell surface,” he said. “The key here is that it’s capturing the mutated antigens that are specific to the patient’s own disease. This is, we believe, the downfall of other approaches that rely on off-the-shelf, so-called cancer antigens, because those are self-antigens that we all have in us. They just happen to be overexpressed in certain tumor types. This is why, we believe, no one has ever seen a direct correlation between immunity to one of those antigens and meaningful clinical benefit.” The immune response is just not strong enough to damage the tumor, Abbey said.

‘In a Position to Go It Alone’

“From that one leukophoresis and tumor sample, our production process gives us, on average, five years of dosing, and the final product is frozen,” which is what allows Argos to conduct a global trial from the U.S. Treatment is simple, too. “A patient comes in when they’re going to see their oncologist anyway, gets an injection and walks out,” Abbey said.

The 450-patient trial is comparing overall survival in patients given Sutent (sunitinib malate, Pfizer Inc.) and whatever treatment may follow Sutent vs. patients given the same regimen plus nontoxic AGS-003. “Having something that can be combined [with existing kidney-cancer therapies], with a completely different mechanism of action, would be a great place to play,” Abbey said.

“It turns out, we got a little bit lucky,” he said. “Published data came out in a Phase II trial – not by us, but by Cleveland Clinic – showing that Sutent has an off-target effect that benefits immune therapy, in that it actually, in many patients, decreases regulatory T cells and myeloid-derived suppressor cells. It’s making the environment in the patient more amenable to immune intervention.” Other agents, such as platinum-based chemotherapies, also “have off-target effects that are synergistic with cellular-based immunotherapy, like dendritic-cell therapy,” Abbey said. “That’s a study that’s now a year and a half or two years old, and has been confirmed by other groups.”

Median overall survival with existing therapy for the intermediate- to poor-risk patients targeted by Argos is 15 months, a rate confirmed in data presented this year at the American Society of Clinical Oncology meeting. Against that, Argos’ median survival of 30-plus months in Phase II trials “looks quite striking,” Abbey said. A third of the patients from that experiment are alive after more than four years, some approaching five years and longer, a “fairly remarkable” outcome, he said, given that standard of care likely would result in less than 5 percent survival at four-plus years.

“It’s clear that something very good is happening in these patients that can only be explained by our product,” Abbey said. “Obviously, we have to prove that in Phase III. We’re confident that we have a great chance of success.”

There’s also an HIV program testing AGS-004, with Phase IIb data due in the first half of next year. “We believe we have a shot at eradicating the virus in some patients,” using combination therapy, Abbey said.

Partnering may or may not happen. “We’re going to be in a position to go it alone,” he said. “When we launch commercially, it will be using an automated manufacturing process in a commercial facility,” so the cost would be similar to that of making a biologic. “We will certainly continue those partnering discussions as we get farther along in Phase III, and think about other regional deals, and potentially U.S. or global deals, if it makes sense.” n