Indication: Biliary tract cancer, gastric, colorectal and breast cancer
Varlitinib (ASLAN001) is a small molecule based reversible pan-HER inhibitor of EGFR (IC50 = 7 nM), HER2 (IC50 = 2 nM) and HER4 (IC50 = 4 nM). In response to the binding of various ligands, these kinases undergo heterodimerisation and homodimerization, resulting in activation of numerous growth factor signalling pathways. 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. Licensed from Array BioPharma with global rights for all indications, varlitinib is being developed as first-in-class drug for biliary tract, gastric and colorectal cancer, and as best-in-class drug for breast cancer.
A phase 1b study for combined therapy of varlitinib and doublet chemotherapy continues to deliver impressive data in a number of difficult-to-treat tumour types. Data in animal models have shown that the drug may also be effective in hepatocellular carcinoma.
It has been studied in more than 300 patients with good tolerability.
Varlitinib has received Orphan Drug Designation for cholangiocarcinoma and gastric cancer by the US Food & Drug Administration. It has also received orphan status for biliary tract cancer by the Korea FDA.
ASLAN is also collaborating with Hyundai Pharmaceuticals to develop and commercialise the drug in Korea.
A pivotal trial in second line BTC is currently in progress. A first line study is also being initiated. Varlitinib has demonstrated excellent tumour shrinkage and disease control in combination with chemotherapy and as monotherapy. There are currently no effective approved therapies to treat BTC.
ASLAN has successfully completed a phase 2a study in subjects with tumours that upregulate both the HER1 and HER2 proteins on their cell surface. This population represents 40% of gastric cancer incidences. The study shows good evidence of pharmacodynamic activity in gastric cancer with strong inhibition of downstream kinases and induction of apoptosis and inhibition of proliferation.
The HER-family of receptors has been a key target for the development of anti-cancer therapeutics. In gastric cancer, approximately 10% of tumours have amplification of the HER2 gene, and trastuzumab (Herceptin®), a HER2 specific monoclonal antibody, has been shown to demonstrate clear clinical benefit in this group. However, in gastric cancer and other tumour types, there are many tumours that are driven by other members of the HER family that are not eligible for treatment with a HER2-selective agent. Therefore, there exists a significant unmet need for these patients, most of whom receive chemotherapy and often a poor prognosis.
ASLAN is completing a phase 2 study in breast cancer. Data shows varlitinib activity in mBC as both monotherapy and in combination with chemotherapy.
Varlitinib has demonstrated remarkable anti-tumour activity in patients with no treatment options as their tumours have progressed on all standard of care therapies.
ASLAN has partnered with Array BioPharma Inc for the development of varlitinib (ASLAN001). Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small-molecule drugs to treat patients afflicted with cancer and inflammatory diseases. Array’s proprietary drug development pipeline includes clinical candidates that are designed to regulate therapeutically important target proteins and are aimed at significant unmet medical needs. To learn more about Array, please visit www.arraybiopharma.com.
ASLAN has partnered with Hyundai Pharmaceuticals to develop and commercialise varlitinib (ASLAN001) in South Korea. Founded in 1965 HYUNDAI Pharm Co. Ltd., with its base in Seoul, Korea, is a pharmaceutical company specialised in modern medicine. HYUNDAI is a leading expert in various therapeutic categories, including CV and respiratory system, and the company is expanding into additional areas including women’s health, CNS, and oncology. HYUNDAI engages in manufacturing and sales of more than 200 products in prescription medications, OTC medications, FDA-approved hair loss treatments, and health functional beverages. Concurrently, HYUNDAI is investing in pharmaceutical product development, most recently in the in-house development of novel Type II diabetes molecules, as well as co-development agreements with foreign biotech companies and universities. To learn more about HYUNDAI, please visit www.hyundaipharm.co.kr.