For VBL Therapeutics Inc., positive interim top-line phase II data with its gene therapy for recurrent glioblastoma took the sting out of February's news with a separate compound targeting psoriasis and ulcerative colitis, also each in a phase II trial.

Shares of Tel Aviv, Israel-based VBL (NASDAQ:VBLT) closed Wednesday at $7.22, up $1.63, or 29.3 percent, as investors cheered statistically significant interim top-line results from the ongoing brain cancer experiment, in which VB-111 yielded an improvement in overall survival (p = 0.05) in patients given the drug as a standalone and those who got the gene therapy plus Avastin (bevacizumab, Roche AG), compared to patients treated with Avastin alone when their disease progressed.

When VB-201 fizzled earlier this year, Wall Street trimmed VBL's shares by 65.5 percent, knocking them down to $4.87, more than a dollar under the company's IPO price in the fall of last year, when the company sold about 6.6 million shares at $6 each to raise $40 million. The IPO was hard won, as the firm's previous attempt was tripped up after a U.S. shareholder did not fund payment for shares as promised. (See BioWorld Today, Feb. 18, 2015.)

Things are looking up with VB-111, which emerged from VBL's Vascular Targeting System platform, designed to take aim at angiogenic blood vessels. The approach can be tailored to either destroy them or promote their growth, VBL said, with special efficacy in endothelial-cell gene expression. Officials at the company could not be reached, but in a press release the firm said that full results will be disclosed at the American Society of Cancer Oncology (ASCO) meeting in late May and early June in Chicago.

The interim data include 46 patients. VB-111 monotherapy was discontinued upon disease progression in 22 who were then treated with Avastin by itself. Another 24 patients, when their tumors advanced with VB-111 monotherapy, could choose to get further treatment with the drug combined with Avastin. Twenty-three patients have gotten the combo therapy, and one is still stable on VB-111 monotherapy at 424 days. So far, the upshot is that VB-111 in combination with Avastin gained a median overall survival of 414 days, compared to 235 days in patients on VB-111 followed by just Avastin (p = 0.05).

VBL has said top-line data show the same drug in a phase IIa study against recurrent, iodine-resistant differentiated thyroid cancer brought disease stabilization plus a good safety profile in patients who had progressed after several lines of treatment. In glioblastoma, the FDA has lifted the partial clinical hold as of February, and is allowing the pivotal phase III trial to go ahead under a special protocol assessment.

MANY PLAYERS, SOME SUCCESS

At the time of the February failure of VB-201, Deutsche Bank analyst Alethia Young held out hope for VB-111. "The partial [clinical] hold was mostly administrative related to manufacturing," she noted in a research report. "We model peak sales of $390 million in 2025 and assume a 2017 launch." Young was "focused on the timelines, as the company has quite a low cash balance," ending 2014 with about $36 million, an amount that VBL estimated "should be enough cash to get it to the interim look in 2016 for VB-111, but not to the end of the trial," Young wrote.

Regarding VB-201, her firm "did not assume any probability of success in autoimmune diseases," even though the stock got walloped by the bad psoriasis/ulcerative colitis news. Young maintained a 75 percent likelihood of an ultimate win with VB-111 in glioblastoma. VBL also intends to present data with the compound in ovarian cancer during the ASCO meeting.

Young weighed in on the latest outcome as well, which confirmed her optimism. "Timelines remain on track for the [phase III] trial to start in mid-2016," she wrote in a Wednesday report. "Avastin has had highly variable survival data in the past because of the severity and heterogeneity in treatment of glioblastoma. Many cancer trials fail in phase III, and we caution given the small size of this phase II in a highly variable population. However, we do see these data as encouraging," and Young kept her probability-of-success estimate at 75 percent.

VBL's phase II glory in the tough brain cancer indication recalls Lexington, Mass.-based Agenus Inc.'s win against newly diagnosed disease with the autologous heat-shock protein vaccine Prophage, another potential weapon in the arsenal against a tumor that usually kills within one year. Prophage gained a median overall survival of about 24 months when combined with standard of care, with 33 percent of patients alive at two years and still being followed for survival. (See BioWorld Today, July 2, 2014.)

VBL and Agenus are hardly alone in glioblastoma, with Cortellis Clinical Trials Intelligence listing 69 phase II trials currently recruiting. Among phase III studies, eight are enrolling patients. Other developers in the space to gain attention from analysts lately are Genspera Inc., of San Antonio, which has mipsagargin, made of the plant-derived cytotoxin thapsigargin and designed to take apart solid tumor vasculature, in an investigator-led phase II study at the University of California San Diego, and Natick, Mass.-based Karyopharm Therapeutics Inc., with selinexor, described as a first-in-class selective inhibitor of nuclear export, expected to report phase II data this year. Expected to start a phase III trial in newly diagnosed glioblastoma in 2015 is Immunocellular Therapeutics Ltd., of Calabasas, Calif., which has ICT-107, a dendritic cell-based vaccine that faltered in an exploratory phase II test in 2013 but may have legs. (See BioWorld Today, Dec. 13, 2013.)

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