Considering its relatively inconspicuous presence in the body, the pancreas can wreak havoc on human health through two major diseases: diabetes and pancreatic cancer. Both can be deadly – the former from the condition itself or from long-term complications and the latter from advanced disease that may be symptomatic for only months or even weeks. Neither has a cure.
Pharmacyte Biotech Inc. aspires to change that bleak prognosis with a technology that can attack both culprits.
The Silver Spring, Md.-based company was founded in 1996 as Efood Systems, which tracked the movement of refrigerated trucks, before morphing into a natural products firm and eventually changing its name to Nuvilex Inc. In early 2011, the company established a relationship with the inventors of an unusual encapsulation technology with the idea of moving into nutraceuticals.
Poor financial decisions nearly derailed the company, which restructured again last year, assembling a new leadership team and taking direct aim at the biotech market with the live cell encapsulation platform, known as Cell-in-a-Box. Ken Waggoner, president, CEO and chairman of Pharmacyte, said the team “brought the technology back from the dead” and is eager to see the platform to fruition in multiple therapeutic applications.
Cell-in-a-Box technology involves the encapsulation of living cells in protective “cocoons” – capsules that are visible to the eye at about the size of the head of a pin. The capsules prevent the cells from escaping into the body while keeping the immune system from invading.
The multi-step encapsulation process begins with the suspension of the live cells in a medium that contains a polymer and sodium cellulose sulfate. That suspension is passed through specialized equipment to form droplets, which fall into a solution containing a second polymer. When the polymers interact, a membrane forms around each droplet, ultimately developing into the protective shell.
An important distinction between the capsules produced through Cell-in-a-Box technology and those fabricated by potential competitors is Pharmacyte’s use of cellulose – a bio-inert material that doesn’t prompt an immune system response – rather than substances such as the seaweed derivative alginate or chitosan.
“The Cell-in-a-Box capsules can withstand various external forces, unlike those made using other encapsulation methods,” Waggoner said, enabling Pharmacyte’s capsules to be implanted intact using needles or catheters. “Our capsules don’t degrade, even after being present in the body for over two years, and they don’t cause damage to, or inflammation of, nearby tissues in the body.”
In the lead pancreatic cancer indication, approximately 300 Cell-in-a-Box capsules that each contain some 10,000 cytochrome P450-expressing cells are placed as close as possible to the tumor site, then one-third the normal dose of the chemotherapeutic ifosfamide is injected systemically. When the capsules and the chemotherapeutic come into contact, the encapsulated cells convert ifosfamide at the site of the tumor, providing a high concentration of the cancer-killing agent without the traditional side effects of high-dose chemotherapy.
Pharmacyte acquired exclusive global rights to the technology from Austrianova Singapore Pte. Ltd., of Singapore, in all cancer indications and in diabetes and also holds rights to use cancer prodrug-activating cells as part of the treatment protocol for advanced pancreatic and other cancers. The Cell-in-a-Box capsules are produced in a cGMP-compliant facility managed by Austrianova.
Pharmacyte is preparing to conduct a phase IIb trial in patients with borderline operable or non-operable pancreatic cancer, expected to begin in the third quarter, that will compare its treatment head-to-head with gemcitabine combined with Abraxane (nab-paclitaxel, Celgene Corp.). In July, the company initiated a second preclinical study in mice to assess the effectiveness of its pancreatic cancer treatment on the rate of accumulation of malignant ascites fluid in pancreatic cancer and other abdominal tumors, testing four separate doses of ifosfamide with the goal of setting parameters for the design of a phase I. Pharmacyte plans to conduct a separate trial, also beginning this quarter, to investigate the role of Cell-in-the-Box in reducing pain associated with tumor growth.
Last year, the FDA granted orphan drug designation to the company’s pancreatic cancer treatment.
In addition to pancreatic cancer, data from an early trial suggested the Cell-in-a-Box technology might have an effect on downstream micro metastatic disease, which could apply to other tumor types. Pharmacyte has initiated preclinical programs in brain and breast cancer, using cannabinoid prodrugs in combination with Cell-in-a-Box. Last month, the University of Northern Colorado, one of the company’s research partners, obtained a Schedule 1 license from the Drug Enforcement Agency, enabling it to begin experiments using cannabinoids.
‘We think we have a shot at curing diabetes’
For treatment of type 1 and insulin-dependent type 2 diabetes, Pharmacyte uses the same Cell-in-a-Box technology but with Melligen cells – a human liver cell line genetically modified to produce insulin on demand that was developed by researchers at University of Technology Sydney, Australia – rather than the more common pancreatic beta-islet cells to serve as a bio-artificial pancreas.
“A lot of companies are trying to do this type of technology with different types of cell encapsulation and different types of devices,” said Gerald Crabtree, Pharmacyte’s chief operating officer. “Nearly all of them are centered around some form of islet cell, but islet cells are notoriously difficult to keep alive for long periods in the body, even if they’re encapsulated.”
The Melligen cells “are easier to keep alive, and that’s the key,” he added.
Pharmacyte holds the exclusive worldwide license to the cell line. Preclinical testing of the diabetes approach is under way through an international consortium the company recently spearheaded.
Although questions about the diabetes indication remain – exactly where to place the capsules in insulin-dependent patients, for instance – “we think we have a shot at curing diabetes,” Waggoner said. “We certainly know we can reverse the condition.”
Of course, the technology first needs to succeed in human studies, and that will take a few years.
“We believe we’ll be able to get into the clinic much sooner than anyone would have anticipated when we started down this path,” Waggoner said. Outside experts predicted the company would need more than five years to move the diabetes program, initiated in April 2014, into clinical trials, but Waggoner is confident that timetable can be truncated to 2017 – perhaps earlier. And, since the pancreatic cancer work is already under way, “by the time we get into the clinic with diabetes, the FDA will know this technology platform,” he pointed out.
In addition to establishing the diabetes consortium, Pharmacyte has been meeting with investors and clinical investigators and conducting road shows in New York, Boston and the Bay Area to “test drive” its message. The company also had a busy dance card at the BIO International Convention in Philadelphia, where it hosted dozens of meetings at its suite in the Ritz-Carlton Hotel.
For the time being, Pharmacyte is comfortably financed through a $50 million at-the-market facility. But with the prospect of large trials looming down the road, the company also is assessing the interest of big pharmas, and many have signed nondisclosure agreements.
“We’ve been approached by a number of people who want to get involved,” Waggoner said. “They’ve recognized that our treatment is very different from any approach that’s out there.” //