The surprise phase III blow-up of Synta Pharmaceuticals Corp.’s heat-shock protein 90 (HSP90) inhibitor ganetespib, disclosed Tuesday night, sent shares into the basement and dealt what one analyst called “a major blow to confidence in the drug,” still in four trials sponsored by investigators and cooperative groups that are testing the compound against other indications.

Synta CEO Chen Schor said the fact that the trial, which had enrolled about 700 of a planned 850 patients, quit for futility “underscores the challenge of treating lung cancer in the second-line setting, a treatment area where few therapies have demonstrated benefit.” He added during a conference call with investors that his firm has “begun the process of an orderly wind-down” of the study, analyzing data further “to determine the path forward, if any” for ganetespib in NSCLC.

Cambridge, Mass.-based Synta saw its stock (NASDAQ:SNTA) nosedive 63.8 percent, or $1.30, to close at 74 cents, as company officials said they are still sifting data from the halted trial, called Galaxy-2, testing ganetespib plus docetaxel. A data monitoring board said the combo, though well tolerated, was unlikely to hit statistically significant improvement in overall survival, the primary endpoint.

“We were wrong,” Roth Capital Partners ‘ Joseph Pantginis wrote in a research report, adding that his firm believes any positive news from other studies with ganetespib “would need to be profound in order to potentially reignite interest in the drug. Until then, the focus will be on to what extent the company will restructure its operations and how it will potentially increase its investment into the HSP90-inhibitor drug conjugates [HDC] platform.”

In September, Synta hired a new chief scientific officer, Alan Rigby, to help advance the HDC effort, yet to enter the clinic. Schor said “there are a few payloads that we’re working on, and asking some very high-bar preclinical questions” of the HDC prospects, and the platform “at this point is getting significant attention to try to find the best candidate.”

In NSCLC, Pantginis had projected a 60 percent chance of success. The compound underwent an earlier phase III experiment, Galaxy-1, in NSCLC. Though the data from that effort disappointed some backers of the firm, the results supported Synta’s selection of patients for Galaxy-2. Other studies are trying ganetespib in breast cancer, ovarian cancer and acute myeloid leukemia. (See BioWorld Today, July 23, 2014.)

Results from the other experiments are due in 2016 and 2017, though Schor could not be more specific. “We’re working in a very collaborative manner” with the sponsors of the trials, adding that “we cannot control the enrollment for these studies,” some of which may report “sooner rather than later.”

Synta had little to say on the somber conference call Wednesday morning, but in an August earnings call sounded enthusiastic, like others, about ganetespib’s prospects when paired with promising new therapies. Vojo Vukovic, chief medical officer (CMO), noted that the firm has “two collaborations and also internally conducted a number of preclinical studies to evaluate the feasibility of combining with different immunotherapies, including checkpoint inhibitors. These collaborations have produced encouraging results which have generated a lot of interest and enthusiasm with investigators. And we’re currently in discussions, multiple discussions about potential studies in the clinic, and we’ll provide updates as soon as we can.”

The company ended the second quarter with cash and cash equivalents of $98.3 million.

Also at the time of second-quarter earnings, Cowen and Co. analyst Boris Peaker repeated Synta management’s assertion that “the interim look is well powered and that if Galaxy-2 behaves like Galaxy-1, they believe the trial has a good chance of stopping early for efficacy,” though he added that “we don’t expect this to occur.” It didn’t, though what did occur blindsided many.

Peaker wanted to know during the most recent conference call if Synta might invest in the other ganetespib trials to expedite them, but he didn’t get an answer and turned his attention to the HDC platform, asking when data will emerge. “We do have significant preclinical data with one of the compounds,” Schor said, while others await more testing. “We’re getting ready to file an investigational new drug application, and potentially will be in the clinic next year,” he said.

Meanwhile, CMO Vukovic said Synta “will do our best to analyze the [latest ganetespib] data in a comprehensive manner. We’ll also look at tumor samples we collected. We’ll try to extract as much information as possible, for one, to understand what happened in Galaxy-2, and secondly to really help optimize the ongoing [trials] or enable any potential future studies with ganetespib.”