Magazine Article | September 8, 2017

Reaching A Turning Point With An Unusual Cancer Therapeutic

Source: Life Science Leader

By K. John Morrow Jr.

Sometimes it pays to go against the grain. In 2013 Life Science Leader published an article describing the efforts of Dr. Ray Takigiku to establish Bexion Pharmaceuticals, a startup biotechnology firm, located in Covington, KY.

Bexion was one of a number of infant biotechs housed under the guidance of BioLogic, a biotechnology incubator, which has since been reconfigured as a nonprofit umbrella operation. Bexion’s headquarters in Covington was taken over by SIDIS, a private investment management company, which continues to lease out the space to several companies, including Bexion.

Takigiku, president and CEO of the company, ignored the conventional rules of biotech startup development in a number of ways. First, Covington is far from the regular biotech hot spots on the East and West coasts of the U.S. This proved to be an auspicious choice, as the company received $500,000 from the state of Kentucky’s SBIR-STTR Matching Funds Program.

Secondly, the company chose to renovate a 19th century warehouse rather than build a sparkling new structure from the ground up. Because of the complexities of historic renovations, this approach may drive up the final price tag of the real estate, but does deliver a one-of-a-kind architectural effort. Finally, Takigiku’s top choice for a hot new therapy was not a standard chemotherapeutic drug that poisons cancer cells, but rather a substance that appeared to trigger their programmed destruction, or apoptosis.

In a recent interview, Takigiku looked back on the events of the last four years as he pursued his “extraordinary idea” that he believed would drive the company forward. During this period, the dozen or so members that make up the Bexion staff have made substantial progress on the development of a therapeutic agent with the present designation of BXQ-350. This substance is composed of two disparate molecules built into a structure known as a nanovesicle. When joined together, those molecules form a potent anti-tumor complex. Cancer cells, unlike normal cells, display negatively charged phospholipid molecules on their cell surfaces. These phospholipids, such as phosphatidylserine, strongly bind the highly toxic nanovesicles. Takigiku and his colleagues hypothesized that the nanovesicles would eliminate cancer cells and leave their normal, nearby companions unscathed. In earlier studies Bexion scientists showed that BXQ-350 killed tumor cells in culture and eliminated human tumors grafted into a special strain of mouse.

With the encouraging results from the preclinical work, Bexion has moved to Phase 1 cancer trials, which are authorized by the FDA to consist of a small number of patients, usually in the range of 10 to 30, although in some cases as many as 100. These trials provide an assessment of doses that can be tolerated by the patient without unacceptable toxicity. The therapy will be targeted at patients suffering from glioblastoma, although a Phase 1 trial may accept participants with unrelated conditions. Glioblastoma multiforme is a highly aggressive cancer with an extremely poor prognosis. “We have 10 patients enrolled in our first Phase 1 trial, and we will enroll six more in the coming month or two,” Takigiku says. “At this time I can confirm that the pharmacokinetics are as predicted, and the safety profile is promising.”

The company is moving ahead aggressively and planning an expansion phase with 30 additional patients. Assuming that portion of the trial generates positive data, Takigiku is hoping to move to a Phase 2 clinical trial sometime in the next calendar year.

Given the very long lag times involved in drug development, many biotech companies struggling in the midst of a new therapeutic modality look to marketing parts of their technologies to generate bridge income. Takigiku recognizes that as a possible avenue for funding.

“We believe our technology has multiple legs, and there are unexploited leads for us to pursue,” he says. “Because of the rapid progress in this area, we are examining these opportunities on a day-to-day basis. We are especially interested in multiple tumor types, as we believe phosphatidylserine is a ubiquitous target in solid tumors. This property bolsters our confidence in its application as a general delivery agent.”

Takigiku raised startup funds initially through a group of private investors, which relieves the pressure of an immediate payback from his technology. “We are fortunate to be adequately funded, and as such, we have the luxury to focus on our long-term goal of moving BXQ-350 through clinical trials and to a final approval.”

Expanding on his previous comments, he adds, “We now have a defined set of priorities [e.g., all research is focused on cancer] as we move our research forward. We also have the usual interests, such as predictive biomarkers, or other ways to potentially stratify patients.”

The cancer research community, including Bexion, is trying to adapt to the overwhelming focus on the immune system and its manipulation, especially the proteins known as checkpoint inhibitors. These are quite the rage these days as investigators seek to exploit weak points in the cancer cell’s wall of defenses. In recent years it has been discovered that this class of proteins, whose function is to dampen the immune response, can prevent the interaction of the T cells and dendritic cells to destroy tumor cells. This elaborate system of checks and balances ensures that the patient’s own immune system won’t overreact and destroy normal tissue. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to attack and kill cancer cells. A major area of cancer research today involves the use of proteins that block the checkpoint inhibitors, and with two negatives equaling a positive, the T cells are released and mobilized to destroy cancer cells. Monoclonal antibodies that block the interaction between the programmed cell death (PD)-1 protein and one of its ligands, PD-L1, trigger dramatic anti-tumor responses.

With everything that’s going on in cancer research today, Takigiku thinks of present-day therapy as a symphony of responses, in which a number of dissimilar strategies will be combined. “We are focused right now on getting into Phase 2 and in global registration,” he offers. “Today there are lots of miracle stories that do provide hope. We want to follow these and be hopeful — but not stupidly hopeful.”