With the bulk of Galena Biopharma Inc.'s value riding on cancer vaccine Neuvax (nelipepimut-S), the firm's shares predictably plunged to a new 52-week low Wednesday as an independent data monitoring committee (IDMC) recommended the PRESENT phase III study in breast cancer be stopped for futility following a planned interim analysis. But it's the troubling language in the IDMC's letter, suggesting the placebo arm might actually have bested the treatment arm, that could signal the end of the road for Neuvax.

That seemed to be the way investors interpreted the news. Galena's stock (NASDAQ:GALE) fell $1.68, or 82.8 percent, to close at 35 cents, with shares trading at nearly 26 times their normal volume.

Details will be forthcoming later. Galena President and CEO Mark Schwartz said the San Ramon, Calif.-based firm will likely hold a conference call next week, after it has had a chance to evaluate the data, which, as of Wednesday, still remained blinded to the company.

Initiated in early 2012 under a special protocol assessment agreement with the FDA, PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) enrolled a total of 758 patients, specifically a subpopulation identified as having low to intermediate expression of HER2 (immunohistochemistry levels of 1+ or 2+) and HLA A2-positive and/or A3-positive status, and tested Neuvax as an adjunctive therapy to prevent cancer recurrence. The primary endpoint is disease-free survival (DFS) at 141 events. A futility interim analysis was scheduled at 70 events, a milestone Galena hit earlier this year. (See BioWorld Today, June 26, 2009.)

Investors were hoping for, as Roth Capital Partners analyst Joseph Pantginis wrote earlier this year, "a 'non-event' continue-as-planned announcement," but that was not to be the case.

Even more disturbing, the IDMC noted in a brief letter, disclosed in a company 8-K filing, that the study should be discontinued for futility "unless it is determined that there has been a systematic reversal in the study drug treatments in the two arms, in which case the IDMC should reevaluate the clinical evidence." The letter urged Galena to investigate that possibility "as quickly as possible."

Galena execs declined further comment at this time.

Neuvax comprises an E75 peptide from HER2 and immune adjuvant GM-CSF, designed to stimulate CD8-positive T cells to target cells expressing HER2, with the idea that the immunotherapy could be effective regardless of whether patients expressed low or high levels of HER2. As a comparison, HER2-positive breast cancer staple Herceptin (trastuzumab, Roche Holding AG) is typically used to treat women whose tumors express high HER2 levels.

PRESENT was designed specifically to enroll patients with low to intermediate HER2 expression. The off-the-shelf product is given intradermally as a once-per-month injection, with a subsequent booster every six months, following standard of care, including surgery, chemotherapy or radiotherapy.

Besides PRESENT, Galena is testing Neuvax in two studies in combination with Herceptin. A phase IIb trial is enrolling node-positive, triple-negative HER IHC 1+/2+ patients, and a phase II trial is testing the combination in high-risk, node-positive or negative HER2 IHC 3+ patients. The company had been planning additional trials of Neuvax in ductal carcinoma in situ and in gastric cancer, but whether those studies will proceed as planned is now anyone's guess.

The news is particularly disappointing for Galena, which completed a much-needed course correction last year. It divested a commercial operation – Abstral (fentanyl) sublingual tablets and Zuplenz (ondansetron) oral soluble film – acquired two years earlier in an ill-fated effort to add revenue while awaiting the outcome of the years-long PRESENT study. And in late 2015, Galena reached a settlement agreement in a securities class action that had accused former execs of misleading marketing and insider trading.

Focus narrowed to Neuvax and the PRESENT study, and investors anticipating a continue-as-planned recommendation pushed the stock up more than 100 percent since March when the DFS event was reached.

With shares now trading below $1, the firm's chances of fundraising have declined. Galena ended the first quarter with about $34.7 million in cash and equivalents. It added $23.4 million through a debt offering in May.

If further development on Neuvax is halted, Galena has earlier-stage programs, including GALE-301 and GALE-302, two cancer immunotherapy peptides derived from folate binding protein that earlier this month gained orphan designations in ovarian cancer. GALE-301, an E39 peptide, is in the phase IIa portion of a phase I/IIa trial in ovarian and endometrial adenocarcinoma. GALE-302, which is an attenuated version of GALE-301, is in testing sequentially with GALE-301 in a phase Ib trial in breast and ovarian cancers.

Also earlier this month, Galena reported positive safety data at the European Hematology meeting for GALE-401, a controlled-release version of platelet-reducing drug anagrelide, in thrombocytopenia secondary to myeloproliferative disorders.