Scientists have long been fascinated by curcumin, a naturally occurring chemical found in the root of turmeric, a plant known as Curcuma longa. The compound is known to have antioxidant and anti-inflammatory properties, but traditional use has been limited to topical and gastrointestinal indications because oral bioavailability is negligible.

Sign Path Pharma Inc. hopes to realize the compound's larger medicinal potential – initially, in cancer – by delivering a liposomal formulation intravenously.

Established in 2006, the Quakertown, Pa.-based company worked quietly to complete preclinical studies in three intravenous formulations, according to Lawrence Helson, Sign Path Pharma's president, CEO and sole employee.

"It was not the most propitious time," Helson admitted. "Right after that, the market fell apart."

Still, with indications of efficacy in multiple diseases, the most advanced formulation – a liposomal curcumin in-licensed from M.D. Anderson Cancer Center – is in the final weeks of a year-long Phase Ia study in healthy individuals, with plans to move later this summer into a Phase Ib dose-finding study in 15 patients with refractory cancers.

Helson, a pediatrician with a 20-year tenure at Memorial Sloan Kettering Cancer Center and previous affiliation with several biotech start-ups, hopes to move the compound, known as Lipocurc, into a Phase II trial in the fourth quarter, targeting lung or pancreatic cancer as the initial indication.

Lipocurc, the first curcumin derivative formulated for intravenous delivery, has shown the potential to address multiple billion-dollar markets in cancer, neurodegenerative disease, diabetes drug resistance and drug-induced cardiotoxic adverse events, Helson said, with concentrations of total curcumin and its main metabolite, tetrahydrocurcumin, sufficient to interfere with the growth of cancer cell lines and neurologic disorders.

Funding, the principal limitation, forced the company to concentrate on one indication and one study at a time.

"We could do others, because this drug, so far, works in hundreds of diseases," Helson told BioWorld Today. "I'd love to do idiopathic pulmonary fibrosis – black lung disease – which affects about 200,000 people in the States, but we're moving as fast as we can with the money we have."

Preclinical and early Phase Ia data suggested significant differences between two- and eight-hour Lipocurc infusions with respect to the distribution of curcumin in tissues and the metabolism to tetrahydrocurcumin. The studies also suggested the highest distribution of curcumin occurs in lung tissue.

Those findings are important, Helson explained, because curcumin is unstable in the presence of light and alkaline conditions, so it degrades during the detection process and spurious measurements in blood can lead to misinterpretations of bioavailability. Sign Path developed, validated and patented a method to determine total curcumin and tetrahydrocurcumin in body fluids and tissues.

Lipocurc, which is processed from 99.2 percent pure synthetic curcumin rather than extracts, caused no acute toxicity in dogs during two- and eight-hour intravenous infusions at 10 mg/kg, a dose that provides a therapeutic level of the drug.

"So far, we've gone fairly high, and we have no toxicity," Helson said. "We know from the animal studies that [Lipocurc] doesn't affect normal tissues."

To minimize costs, initial trials were conducted in Austria, where the lipocurcumin formulation is manufactured, with approval from the European Medicines Agency.

The Phase Ib and 75-patient Phase II study will be conducted in collaboration with the Central European Society of Anticancer Research, at roughly one-tenth the cost of running the same trial in the U.S., Helson said.

To date, the company has raised about $4 million, including one grant from the Michael J. Fox Foundation for a Parkinson's disease study. Eschewing government grants due to complexity and tardiness, Sign Path Pharma has raised the lion's share of funding from high net worth individuals – about 75 investors in all. Funding rolls in slowly but steadily, Helson said, and the company has no debt.

Sign Path Pharma conducted a pre-investigational new drug (IND) registration submission with the FDA in 2009 and plans to file an IND, using Phase I data, once the compound moves into Phase II. The cost of filing – about $40,000, Helson estimated – offers no benefit to the company before that time, he said.

Sign Path Pharma also has filed paperwork with the SEC to operate as a public entity but plans to remain private at least until Lipocurc is in Phase II studies.

In the meantime, the company's two additional in-licensed curcumin formulations – a polymeric nanocurcumin known as Nanocurc from Johns Hopkins University School of Medicine and a slow-release liposomal-PLGA-curcumin known as Depocurc from the University of North Texas Health Science Center – have shown initial efficacy in preclinical studies but sit on the sidelines while the company focuses on Lipocurc.

Sign Path Pharma's license agreements cover patents and intellectual property on the three formulations.

Long term, the company hopes to attract partners, though it faces the same conundrum as other small biotechs.

"We've been approached by multiple big pharmas, but all of them say, 'When you're in Phase II and you get results, call us,'" Helson said. "'We'll give you whatever you want at that time, but we can't afford any risk.'"