Briacell Therapeutics Corp. hasn't exactly advanced its only asset, Briavax, with lightning speed. Instead, the cancer vaccine sat on the shelf for much of a decade while its inventor, Charles Wiseman, an oncologist affiliated with St. Vincent Medical Center in Los Angeles, tried to scrape together funding.

Now, following two phase I studies, the FDA cleared the company to begin an open-label phase I/IIa trial of Briavax in patients with advanced breast cancer. The genetically engineered whole-cell vaccine is derived from a human breast tumor cell line. The open-label trial, also designed to help establish the company's companion diagnostic, Briadx, is expected to enroll up to 24 late-stage breast cancer patients with recurrent and/or metastatic disease who will receive Briavax every two weeks for a month, then monthly for up to one year.

Safety data from the first nine patients are expected by year-end.

Although the trial is designed primarily to evaluate safety, a principal secondary objective is to evaluate tumor size reduction. Briacell, based in Vancouver, British Columbia, with R&D in Berkeley, Calif., also will monitor tumor response and evaluate progression-free survival and overall survival.

Findings, if positive, could "give new life to the field of whole-cell cancer vaccines," observed Bill Williams, who joined Briacell last year as president and CEO.

Williams explained that Wiseman, who co-founded Briacell and remains on its board of directors, experimented with a number of cancer vaccines while a researcher and clinician at St. Vincent and, before that, at the University of Texas MD Anderson Cancer Center. Wiseman's approach was to isolate a tumor from a patient, growing out a cell line and then using the irradiated cell line to vaccinate other patients with similar cancers.

When an initial treatment regimen in 14 patients using a breast cancer cell line named SV-BR-1 didn't yield any responders, Wiseman took the cell line and transfected in the gene encoding Granulocyte-macrophage colony-stimulating factor (GM-CSF), using the so-called Gvax strategy. He then treated three additional breast cancer patients and one with ovarian cancer, with the thought that the two cancers sometimes shared antigens. Median survival for the four patients was nearly three years.

One metastatic breast cancer patient had a particularly "remarkable" response, Williams said, resulting in shrinkage of the primary tumor and metastatic sites following three months of treatment. Although the patient was in nearly complete remission, the protocol at the time only allowed for six treatments over approximately five months. When she came off therapy, the cancer recurred, including new metastases in the brain.

Wiseman then received permission to repeat the treatment, administering 10 doses across a schedule of alternating weeks. Initially, the patient again enjoyed another nearly complete remission until the cancer recurred and she came off the study.

Still, to have a patient respond twice to the cancer vaccine "was very intriguing," Williams told BioWorld Today.

'Scientifically, we know where we want to go'

When Wiseman couldn't get additional funding through academic channels, he placed the asset and its intellectual property into Briacell. Development remained nearly at a standstill until 2014, when Wiseman connected with Saeid Babaei, a serial entrepreneur and current co-founder, president and CEO of Abcelex Technologies, a vaccine development firm. Babaei, who chairs Briacell's board of directors, engineered Briacell's reverse merger with a Canadian mining shell that resulted in a listing on the Toronto Stock Exchange's Venture Exchange, a concurrent financing with Ansell Capital Corp. and a brokered private placement with Sunel Securities Inc. and M Partners Inc. for gross proceeds of approximately C$2.2 million (US$1.93 million).

"Since that time, [Wiseman] has been busily trying to get this back into the clinic," Williams said.

In the meantime, Briacell hired Markus Lacher as senior director of R&D. Lacher previously served as senior clinical scientist of R&D at Cesca Therapeutics Inc., an autologous cell therapy company where he helped oversee the bone marrow transplantation program, and scientist at Biotime Inc. and subsidiary, Oncocyte Corp., where he developed key components of the company's therapeutic and diagnostic technology.

Lacher characterized SV-BR-1 molecularly and then conducted human leukocyte antigen (HLA) typing on patients who had received the vaccine.

"He found that the one patient with the remarkable response had a double match, at HLA-A and HLA-DR-beta-3," Williams said. "That gave us a clue that, perhaps by doing HLA typing on patients, we may be able to predict who's going to be most likely to respond."

For now, the company isn't limiting trial participants based on their HLA profile, "but we are going to look at that going forward and try to develop the companion diagnostic in parallel with clinical development," he added.

Briacell isn't oblivious to the numerous trial failures in cancer vaccines, such as Curevac AG's mRNA-based prostate cancer vaccine, CV9104; HS-410 (vesigenurtacel-L) from Heat Biologics Inc.; and Galena Biopharma Inc.'s Neuvax (nelipepimut-S). (See BioWorld Today, June 30, 2016, Dec. 2, 2016, and Jan. 13, 2017.)

Briavax is believed to activate the immune system to recognize and eliminate cancerous cells by inducing tumor-directed T cell and, potentially, antibody responses. Wiseman's early findings may have been completely serendipitous, Williams acknowledged. But, he added, Briavax is differentiated from cancer vaccines developed from single antigens or even a single peptide from a cancer antigen.

"That's an interesting approach, but we're using the whole-cell vaccine so there are numerous antigens that are being expressed by our vaccine," he pointed out. "That gives us a distinct advantage."

To date, the targeted vaccine candidate also has been well tolerated with a favorable safety profile – a notable difference from broader checkpoint inhibitors, which can provoke autoimmune responses, Williams said.

"We're very encouraged, but obviously we have a long way to go," he said.

Still, Briacell's premise and early data on Briavax were sufficiently compelling to attract Williams from Incyte Corp., where he served for more than a decade as vice president of exploratory development. Earlier, Williams served as head of experimental medicine and vice president of clinical pharmacology at Glaxosmithkline plc and had an academic career at the University of Pennsylvania, where he ran a research program in receptor biology, including developing bioactive peptides that mimicked GM-CSF.

The virtual company, with just four full-time employees, has approximately C$2.5 million (US$1.88 million) in the bank and plans another capital raise this year. Although the company isn't looking for suitors, it's discussing combination trials with several big pharmas where Briavax could boost response rates of existing cancer therapies without provoking a safety signal.

Briacell also has a second-generation cancer vaccine in development.

"If our current thinking is correct about matching for HLA, probably about 20 percent of patients would have a double match with our current vaccine," Williams said. "But we want to develop it further so we can swap out different HLA molecules in the vaccine" to treat different types of cancer.

"Scientifically, we know where we want to go," he added. "From a business perspective, we're open to different possibilities."