Pancreatic Cancer Drug Granted Orphan Designation

Intezyne Technologies recently announced that IT-139 received orphan drug designation for the treatment of pancreatic cancer. IT-139 is the most advanced GRP78 inhibitor in development for solid tumors, according to a press release.

The orphan drug designation will allow for 7 years of post-approval market exclusivity, FDA assistance, and exemption from Prescription Drug User Fee Act payments.

"Our receipt of an orphan drug designation for IT-139 in pancreatic cancer is an exciting regulatory milestone for Intezyne and a critical step towards clinical advancement of this promising first-in-class therapy addressing an unmet need," said Carolyn Paradise, MD, chief medical officer of Intezyne. "Pancreatic cancer is currently the fourth most common cancer in the US, with approximately 54,000 new diagnoses annually, the majority of which are diagnosed only after their cancer has spread locally and/or metastasized to distant organs. Sadly, pancreatic cancer has proven extremely difficult to treat, with 1-year and 5-year survival rates of only 20% and 8%, respectively — rates which we hope to improve with IT-139."

During a phase 1 clinical trial, patients were administered IT-139 on days 1, 8, and 15 of a 28-day cycle. The primary objective of the trial was to determine the safety, tolerability, and maximum-tolerated dose.

Findings from the trial suggest that the drug is well-tolerated, with patients experiencing manageable side effects, according to the release.

“Since completing our Phase 1 monotherapy trial of IT-139, we have been working with academic collaborators to fully characterize IT-139's mechanism of action — efforts which have yielded exciting results thus far,” said Suzanne Bakewell, PhD, vice president, program manager for IT-139. “IT-139 downregulates the stress-induction of GRP78 in cancer cells, a critical cell survival protein that is associated with both drug resistance and tumor proliferation. GRP78 expression is not elevated in the same way in normal cells, leaving them unaffected."

IT-139 works by targeting the GRP78 pathway that cancer cells rely on to proliferate and survive, which is expected to increase the efficacy of cancer drugs.

Intezyne also reported that preclinical studies demonstrated the drug’s synergy as a combination therapy. The investigators discovered that IT-139 increases the anti-cancer activity of first-line therapies for pancreatic cancer, including taxanes, platinums, and gemcitabine, according to the release.

The investigators also found that the experimental drug demonstrated anti-cancer activity in multiple tumor types, according to the release.

The investigators also found that the experimental drug demonstrated anti-cancer activity in multiple tumor types. IT-139 was observed to have the most substantial effect in pancreatic, liver, and lung cancers, according to preclinical data. Investigators also found that IT-139 inhibits metastasis and reduced gemcitabine resistance in pancreatic cancer.

“Intezyne is currently completing cGMP manufacturing for IT-139 in anticipation of initiating one or more combination Phase 1b/2a studies in 2018,” said Kevin Sill, PhD, CEO of Intezyne. “The synergy with low toxicity observed preclinically in combination with existing anti-cancer agents has already generated considerable attention from both investors and potential strategic partners, a number of whom Russell and I will be meeting this week at the 2017 BIO International meeting in San Diego."