HONG KONG – Aslan Pharmaceuticals Pte Ltd., an oncology-focused biotech company headquartered in Singapore, is set to commence a global pivotal study to treat biliary tract cancer with its lead product, varlitinib (ASLAN-001), after getting clearance from the FDA.

Shortly after, Aslan also received approval from the CFDA to commence a phase II study of varlitinib for the treatment of biliary tract cancer.

Named TreeTopp, the design of the pivotal double-blind, randomized two-arm study was agreed to by the FDA at an end-of-phase II meeting. The study will recruit 120 patients with biliary tract cancer who have failed first-line therapy, and will be conducted in approximately 60 locations across the world, including the U.S., Japan, South Korea, China, Asia-Pacific and Europe. The trial is expected to start in the second quarter of this year, according to Aslan CEO Carl Firth. The anticipated end date for the study has not been disclosed.

The primary endpoint of TreeTopp will be the response rate. Milind Javle, a biliary tract cancer expert from the MD Anderson Cancer Center at the University of Texas, will be leading the study.

"Varlitinib is currently being studied in biliary tract, breast and gastric cancers. The drug has demonstrated good tolerability and safety in our trials," Carl Firth, CEO of Aslan, told BioWorld Today.

Varlitinib is a potent small-molecule inhibitor of the HER-family of receptor tyrosine kinases (RTKs). The type I RTK family consists of four distinct but closely related receptors: epidermal growth factor receptor (EGFR, ErbB1, HER1); epidermal growth factor receptor 2 (HER2, ErbB2); epidermal growth factor receptor 3 (HER3, ErbB3); and epidermal growth factor receptor 4 (HER4, ErbB4). Varlitinib is a reversible inhibitor of EGFR, HER2 and HER4.

"In a large variety of cancers, the overexpression and/or constitutive activation of EGFR and HER2 are often observed and frequently correlate with poor clinical prognosis," Firth explained. "Therefore, by inhibiting the activation of the HER receptors via varlitinib, effects such as shrinkage of the tumor and longer survival can be anticipated.

"Several other companies are studying biliary tract cancer, but to our knowledge there are no other pan-HER inhibitor studies ongoing," he added.

Currently, there is no approved treatment for biliary tract cancer. If study results are positive, varlitinib could go through accelerated approval by the FDA.

"We have agreed with the U.S. FDA that accelerated approval is possible depending on the results of the study," Firth said. "The study results will be meaningful in a number of countries given the general lack of effective therapies in biliary tract cancer."

The U.S. agency also has granted varlitinib orphan designation for cholangiocarcinoma and gastric cancer, and the Korea FDA has recently granted it orphan designation for biliary tract cancer.

Aslan plans to commercialize the drug independently in certain geographies and aims to find commercial partners for other regions, including Europe, Japan and Korea, to assist with local studies and commercialization. The company is already collaborating with Korea's Hyundai Pharmaceutical Co. Ltd. to develop and commercialize varlitinib for cholangiocarcinoma in the South Korean market.

The company will launch an IPO on the Taipei Exchange in mid-May and expects to start trading in early June. The management of Aslan met with investors in Taipei on April 27 to discuss recent developments in the run-up to its planned listing. Some of the capital raised will be used to finance the launch of varlitinib in the market. (See BioWorld Today, Feb. 8, 2017.)

"Aslan has raised $100 million in funds since inception. We have also generated revenues through the out-licensing collaboration agreement with Hyundai Pharmaceuticals, as well as through the acquisition of ASLAN-002, one of our lead compounds, by Bristol-Myers Squibb," said Firth. "These have placed us in a financially strong position to further progress the development of varlitinib. Our IPO will raise additional capital in Taiwan that will take us through to commercialization."

Aslan is focused on the development of immunotherapies and targeted drugs for tumor types prevalent in Asia. The company has offices in Taiwan, China and Australia, enabling it to conduct and support clinical development programs in the region.

In addition to varlitinib, a RON and cMET inhibitor (ASLAN-002) is in phase II development for gastric and breast cancers. Aslan has partnered with Bristol-Myers Squibb Co. to develop ASLAN-002.