Jeff Abbey, president and CEO of Argos Therapeutics Inc., needed all of three minutes to deliver the news that the company was stopping the pivotal phase III ADAPT trial of lead candidate rocapuldencel-T (roca, formerly AGS-003) for futility on the advice of the independent data monitoring committee (IDMC). Abbey did not take questions, and the company said it had nothing to add to a brief statement issued minutes before the call.
An individualized immunotherapy from the company's Arcelis technology platform, roca was being studied in combination with Sutent (sunitinib, Pfizer Inc.) to treat metastatic renal cell carcinoma (mRCC). During a planned interim analysis, the IDMC concluded the therapy was unlikely to show a statistically significant improvement in overall survival (OS) in the intent-to-treat population the study's primary endpoint. The results included 75 percent of the targeted events needed for the primary analysis and OS assessment, according to the Durham, N.C.-based firm.
With AGS-004, the company's personalized immunotherapy for HIV, tripped up during a phase IIb study in 2015, the future for Argos looks bleak. The reckoning was reflected in its shares (NASDAQ:ARGS), which fell to a historic low of $1.25 before closing at $1.48 for a loss of $2.93, or 66.5 percent. More than 6.9 million shares were exchanged, or nearly 36 times the company's three-month moving average.
Roca is designed to capture mutated and variant antigens specific to each patient's tumor and induce an immune response targeting the patient's tumor antigens. ADAPT, which was evaluating roca plus sunitinib vs. sunitinib alone in newly diagnosed mRCC patients, opened in January 2013 and completed enrollment in July 2015, randomizing 462 mRCC patients.
In addition to OS as the primary endpoint, ADAPT was evaluating progression-free survival, tumor response, immune response, safety and pharmacodynamic and other secondary endpoints, according to Cortellis Clinical Trials Intelligence. The IDMC reported that roca was generally well-tolerated in the trial, according to Argos.
Abbey said the company and its scientific advisors are analyzing the preliminary dataset and will seek to meet with the FDA as soon as possible to discuss the findings. ADAPT and investigator-sponsored phase II trials of roca in neoadjuvant RCC and invasive bladder cancer will remain open and patient dosing will be permitted during that time. Once Argos' data analysis and FDA discussions are complete, "we expect to make a determination as to the next steps for the company and for the rocapuldencel-T clinical program," Abbey said.
He predicted the plan forward would be communicated "in a few weeks."
In his final statement, Abbey reiterated his faith "in the ability of precision immunotherapy to improve the lives of patients."
COMPANY HAD PROJECTED CASH THROUGH 2Q
Argos is hardly a new kid on the block. The company, founded in 1997 as Merix Bioscience Inc., traces its roots to Duke University, where its mRNA-based vaccine technology was discovered, and to Rockefeller University, where the company acquired exclusive global rights to complementary technology on a method to generate dendritic cells that became the basis for its Arcelis platform.
Along the way, Argos picked up approximately $17 million in two early rounds, according to SEC filings, before pulling down a $35.2 million series C in 2008 to finance phase II trials of its RCC and HIV candidates. (See BioWorld Today, April 24, 2008.)
In 2011, with a pivotal trial for its mRCC candidate in sight, the company filed for an IPO with a goal of raising $86.25 million. Argos withdrew the filing the following year, opting instead for a $25 million series D. (See BioWorld Today, Aug. 1, 2011, and April 25, 2012.)
The company went back to the private markets a year later to raise a $42.5 million series E, including $30 million from Pharmstandard International SA, the venture arm of Moscow-based Pharmstandard, with thoughts that it might keep the round open and secure additional funds to complete the pivotal phase III ADAPT trial. But in the waning hours of 2013, Argos refiled its IPO, lowering its initial sights to seek $60 million. (See BioWorld Today, Aug. 28, 2013, and Jan. 2, 2014.)
A month later, the company closed its IPO, cutting its share price but upping the number of shares to raise $45 million. The offering was notable more for the fact that it closed the first week of February 2014, a week that saw biopharma IPOs haul in nearly half a billion dollars. (See BioWorld Today, Feb. 10, 2014.)
Other companies from the IPO class of 2014 that folded their tents or are scavenging to remain alive include Bind Therapeutics Inc., Nephrogenex Inc. and Globeimmune Inc. (See BioWorld Today, May 3, 2016, and Nov. 21, 2016.)
In 2015, Argos reported that its HIV vaccine candidate, AGS-004 the other half of the company's Arcelis platform failed to reduce median viral load more than placebo in HIV-infected patients. Though the company, with the support of at least one analyst, deemed some data from the study as validating the agent's potential, the miss spooked investors, sending shares down more than 30 percent. (See BioWorld Today, Jan. 12, 2015.)
Argos completed five small trials of AGS-004 but did not advance the agent into a phase III program. Today, the only active trial is an investigator-initiated phase I/II study testing AGS-004 in combination with the latency-reversing drug Zolinza (vorinostat, Merck & Co. Inc.) for the eradication of HIV in adult patients. The first stage of the trial, which is being conducted at the University of North Carolina, was funded by the Collaboratory of AIDS Researchers for Eradication, or CARE. The Division of AIDS of the National Institute of Allergy and Infectious Diseases at the NIH provided a grant for the second stage of the study.
Argos was clearly pinning its hopes on roca. Last month, the company signed a lease for 32,000 square feet of commercial manufacturing space at nearby North Carolina State University, with reason for optimism. Last June, the IDMC recommended that ADAPT continue, following an interim peek after the trial reached more than half of the targeted number of events to assess the OS endpoint.
At its investor day in December, Charles Nicolette, chief scientific officer and vice president of R&D at Argos, explained the upbeat thesis for the roca technology, noting that "even though we're putting the entire complement of proteins being expressed in the tumor into our dendritic cell, we believe the immune system is targeting only the mutated antigens in the tumor, which plays into the emerging field of people trying to target neoantigens."
In most kidney cancer patients treated with roca, "we observe regression of metastatic disease to at least some extent but we never observe any autoimmune aggression against the normal contralateral kidney," Nicolette added. "So what we have here is an immunotherapy without autoimmunity. And this is engaging the immune system to do what it's supposed to do, which is target specifically things that appear to be non-self."
The low toxicity associated with roca also unleashed the opportunity for combination therapies, he maintained.
As Abbey said, "We have the basis for a very broad franchise in oncology with a unique mechanism of action, with very little toxicity, that we think can be the backbone of immuno-oncology as we move into combination therapies not just in kidney cancer, but in other cancers."
ADAPT likely took the wind out of those sails.
Argos has not reported 2016 year-end financials. As of Sept. 30, the company held cash and equivalents of $69.3 million, which officials had projected as sufficient to fund operations through the second quarter of this year, with the intention of completing ADAPT through top-line data and preparing for commercial manufacturing.