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Argos Snags $25M Series D to Move AGS-003 to Phase III

bwt04252012 Argos

By Marie Powers
Staff Writer

A month after withdrawing its 2011 filing for an initial public offering (IPO), citing poor market conditions, Argos Therapeutics Inc. plied the private pump instead, raising $25 million in a Series D financing to support the launch of its Phase III ADAPT study of AGS-003 in newly diagnosed, metastatic renal cell carcinoma (mRCC).

The financing was led by Forbion Capital and included other existing investors, including TVM Capital, Lumira Capital, Intersouth Partners, Caisse de depot et placement du Quebec, Morningside Group and Aurora Funds.

The company said the study of AGS-003, an Arcelis dendritic cell immunotherapy candidate, will begin this summer under a revised special protocol assessment agreement with the FDA. The pivotal trial will evaluate the addition of AGS-003 to standard therapy compared to conventional treatment alone.

Argos, of Durham, N.C., also disclosed that AGS-003 was granted fast-track designation by the FDA in mRCC.

The Series D was envisioned all along as a backup plan, according to Jeff Abbey, president and CEO of Argos, who said the company disclosed in its SEC filing that existing investors pledged to commit at least $20 million in the IPO. (See BioWorld Today, Aug. 1, 2011.)

Once the company decided to pull the plug on the IPO, the round came together quickly to keep the trial on track, he said.

"It's critical in this environment for small biotechs to have a syndicate from the beginning that can get you to a major value inflection point," Abbey told BioWorld Today.

The proceeds will fully fund the randomized, open-label study of AGS-003 through mid-2013, which should include two-thirds of the planned enrollment of 450 mRCC patients at approximately 100 sites in North America and Europe. The primary endpoint is overall survival (OS), with secondary endpoints of overall response, immune response, progression-free survival and safety.

The company expects to have interim immune response data from the first 40 or 50 enrolled patients by next summer, Abbey said.

The Arcelis technology is designed to personalize RNA-loaded dendritic cell immunotherapies by optimizing a patient's autologous dendritic cells to trigger a tumor- or pathogen-specific immune response. To customize therapy to the unique genetic profile of each patient's disease and the genetic mutations of that disease, Argos loads the autologous dendritic cells with a sample of messenger RNA isolated from the patient's disease, enabling the dendritic cells potentially to precipitate immune responses to the entire antigenic repertoire.

"We take all of the antigens – mutated and nonmutated – so we get a perfect genetic snapshot of the patient's own tumor," Abbey said.

The company's technology also addresses the shortcomings inherent in working with immunosuppressed patients. For example, the Arcelis immunotherapy for cancer equips the immune system to recognize and fight that particular disease, boosting treatment response.

"If your product needs help from a patient's compromised immune system, you're fighting an uphill battle," Abbey observed.

The Phase III trial design for AGS-003 is nearly identical to the company's Phase II study, which enrolled 21 patients with newly diagnosed metastatic clear cell RCC. Treatment consisted of six-week cycles of Sutent (sunitinib, Pfizer Inc.), four weeks on and two weeks off, plus AGS-003 administered as an intradermal injection every three weeks for five doses, then every 12 weeks until progression, in combination with sunitinib.

The Phase II findings, presented during the 2012 ASCO Genitourinary Cancers Symposium in February, indicated median OS of 29.3 months in metastatic clear cell RCC, compared to 15 months for standard of care. As the data have matured, the immune response has extended OS beyond 30 months, Abbey said.

AGS-003 was well tolerated in combination with sunitinib, with no immunotherapy-related serious adverse events. Argos expects to have robust data by next summer, since "we can look at patients after the fifth dose and see a measure of the immune response we're targeting," Abbey said. That mechanism of action is the proliferation of memory T cells that react against a patient's own tumor.

"In the Phase II, the increase in the number of those newly generated memory T cells in patients correlated with overall survival, so it's a prospective way to anticipate survival outcome," he explained.

The Phase II data have generated increased interest from potential partners, which makes a collaboration "a very real possibility for this program," Abbey said. Nevertheless, "that doesn't mean a public financing in the future is out of the question."

Elsewhere in its pipeline, Argos has AGS-004, which continues to enroll patients in an ongoing Phase IIb study in HIV. That trial, which will report data in late 2013 or early 2014, is fully funded by a $21 million contract with the National Institutes of Health.

AGS-009, a monoclonal antibody targeted for lupus, will report Phase I data at the European League Against Rheumatism Congress in Berlin, Abbey said. A fourth candidate, AGS-010, is in preclinical development, with funding from the Juvenile Diabetes Research Foundation.

Argos, which began life as Merix Bioscience in the late 1990s, raised more than $75 million in its earlier rounds. In its IPO filing, the company reported 12.8 million shares outstanding as of June 30, 2011.