Bellicum in Trials with Cancer Vaccine, Cell-Suicide Switches

Xconomy Texas — 

Less than a decade after being hatched out of a Texas university, Houston-based Bellicum Pharmaceuticals is in the midst of clinical trials on two innovative cancer therapies that, if successful, could result in new ways of attacking and killing off harmful cells.

The company uses a platform technology called chemical induction of dimerization, and is in trials on two flagship treatments—a prostate cancer vaccine and a cell-suicide mechanism that can make a currently risky cancer treatment safer to use. In both, immune system cells are implanted with technology that essentially puts an on/off switch inside the cell. A triggering drug, AP1903, flips the switch on, kicking in the desired effect at the right time. AP1903 was created by Massachusetts-based Ariad Pharmaceuticals, which holds an equity stake in the firm and has a licensing deal with Bellicum for the drug.

Bellicum has been on a path of growth in recent years. In March 2012, the company announced a $20 million Series B financing round, with backers including Remeditex Ventures and AVG Ventures. It now boasts a full-time staff of 20—a far cry from the days when chief executive Tom Farrell, who joined the firm in 2006, was the only full-time employee. The company was founded in 2004 by Baylor College of Medicine professors Kevin Slawin and David Spencer.

Its growth may be all the more noteworthy given its success in difficult fundraising times for life sciences startups, as well as its Texas location, which poses unique challenges for budding life sciences companies. The hurdles include the dearth of area venture capital firms that specialize in the industry, certain infrastructure challenges, and the perception that the region lacks management talent, Farrell says. But amid that, Bellicum has raised nearly $38 million to date, all from within the state.

“I’m not saying that it was easy,” Farrell says. The company got a “foot in the door” through initial investors that fronted $10 million needed for Bellicum’s first five years.

To get there, Bellicum had to convince Texas investors more accustomed to bets on real estate and energy to back an innovative cancer treatment startup. In 2011, the firm was helped by a few key pieces of validation. Results of a small but successful clinical trial in young leukemia patients were published in The New England Journal of Medicine, and the Cancer Prevention and Research Institute of Texas (CPRIT) awarded the firm $6.2 million. The award was a double blessing—in addition to the cash, it garnered attention from other investors, with whom CPRIT investigators shared their legwork on Bellicum.

While CPRIT awards were halted amid controversy over alleged conflicts of interest in a grant to a Dallas biotech firm, Farrell credits it with playing an important role in boosting the profile of Texas-based cancer research startups.

“They have an extremely rigorous diligence process—more so than even most venture capital firms,” Farrell says. The award gave Bellicum more credibility with other investors, whose access to CPRIT’s diligence “allayed any concerns about not knowing the space,” Farrell says. Texas legislators are now looking to restore the agency’s funding.

Bellicum attacks bad cells with modified immune system cells implanted with signaling technology that makes them essentially function like on/off switches. The system gives doctors a way to control cells even after they’ve been placed in a patient’s body by administering the trigger drug AP1903, an “on switch” of sorts that activates certain functions of the implanted cell at optimal times.

One such offering is the BPX-501 therapy, which uses Bellicum’s self-destruct switch technology. The treatment is being tested as a way to boost the safety and viability of what’s still considered a dangerous procedure, hematopoietic stem cell transplantation (HSCT). In HSCT, cancer patients are infused with donated T-cells to rebuild their weakened immune systems. But the treatment can go badly awry, even becoming fatal, when the donated cells attack the patient in what’s known as graft versus host disease.

Bellicum addresses this by programming a self-destruct switch into the donated T-cells before they are transplanted. If the patient develops graft versus host disease, he or she can be given AP1903, which triggers the preprogrammed cell—gone rogue and attacking the patient—to kill itself. Bellicum is now aiming to complete by the third quarter of 2014 another clinical trial of the therapy on cancer patients having blood stem cell transplants.

The second of Bellicum’s offerings is its BPX-201 prostate cancer vaccine, consisting of dendritic cells programmed to fight prostate cancer. The vaccine is made from the patient’s own white blood cells, which are embedded with an on/off switch. Doctors wait 24 hours for modified cells to collect in the patient’s lymph nodes before administering the AP1903 that switches on the vaccine. Waiting until the vaccine cells are in the right position “significantly increases” the vaccine’s effectiveness and potency, Bellicum says. The company’s treatment keeps the cancer-fighting effect turned on for longer, producing armies of T-cells able to recognize and attack prostate cancer cells.

Options for prostate cancer treatments have grown since Bellicum first began developing the treatment, which may mean that Bellicum’s treatments become a later—not first—option for patients. While the state of flux in prostate cancer therapies may mean it’s hard to know what competition BPX-201 is up against after it emerges from clinical trials, Farrell says that “in all likelihood,” patients will at some point want to weigh the treatment.

Bellicum has also developed a more powerful, easier-to-manufacture second generation version of the technology. Armed with a fresh round of cash, the company is now focused on follow-on rounds of clinical trials for the commercial versions of its products.

“We’re a small company and we have a fairly ambitious clinical program. The immediate challenge is to execute successfully,” Farrell says.