Varlitinib Ditosylate

Pass and Fail list with a pen. baona/Getty Images/iStockphoto The drug failed to meet the primary endpoints of progression-free survival and overall response rate. Singapore-based ASLAN Pharmaceuticals announced topline data from its TreeTopp (TREatmEnT OPPortunity with varlitinib in biliary tract cancer) trial in second-line biliary tract cancer (BTC). The drug failed to meet the primary endpoints of progression-free survival (PFS) and overall response rate (ORR). Varlitinib is an oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors, HER1, HER2 and HER4. These receptors are mutated or overexpressed in numerous cancer types, resulting in excessive proliferation and uncontrolled growth. The drug has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer. It also received orphan drug designation for biliary tract cancer by South Korea’s Ministry of Food and Drug Safety. The trial was a global, double-blind, randomized two-arm study that enrolled 127 patients who failed first-line therapy. There were 56 sites in the U.S., Europe, Japan, Australia and other parts of Asia. In the trial, the median PFS was 2.83 months for varlitinib in combination with capecitabine compared to a median PFS of 2.79 in the control arm. In the varlitinib arm, ORR was 9.3% compared to 4.8% in the control arm. hbspt.cta.load(4413123, '92ebc33d-a4a8-4c10-b41e-a52c39dc69ea', {}); The trial didn’t hit statistical significance, but Aslan notes that a pre-planned exploratory analysis identified a sub-group with improved efficacy. That analysis was also supported by retrospective review of the JADETREE trial in China, which evaluated the drug in combination with capecitabine in second-line BTC patients. “The results from the study are disappointing,” said Carl Firth, Aslan’s chief executive officer. “They will, however, provide the scientific community with important insights into an aggressive and under-researched disease that presents a growing burden of care worldwide as prevalence arises.” Firth added, “I would like to extend our thanks to the patients, trial investigators and site personnel who participated in the study and to the Aslan team for their commitment to the development of varlitinib. Aslan remains focused on the promising molecules in its portfolio, including the ongoing study in atopic dermatitis of ASLAN004, our IL-13 receptor antibody which blocks signaling through IL-4 and IL-13. We look forward to the interim readout in early 2020.” Biliary tract cancer is a rare cancer of the bile tract, which is the tubes that transport bile produced by the liver into the small intestines. Two bile ducts originate from the liver and one from the gallbladder. They connect to form the common bile duct that connects to the small intestine. When food is digested, bile stored in the gall bladder is released and moves through the bile ducts into the small intestine. Biliary tract cancer can develop anywhere along the bile ducts. Another name for bile duct cancer is cholangiosarcoma. Additional names depend on where on the bile ducts the cancer is diagnosed. It is generally very difficult to treat. The company reported its third-quarter financials on October 29. In addition to the financial information, the company noted that it had presented late-breaking topline data from its Phase II trial in China of varlitinib and capecitabine in second-line BTC at the Chinese Society of Clinical Oncology meeting. In that trials, patients showed a response rate of 11%, including two complete responses, and median progression free survival was 2.7 months and OS was 5.8 months, which was still maturing. They pointed out that patients in the study seemed to present with a more aggressive disease with only 10% of patients responding to first-line gemcitabine-based treatment before enrollment. The company also presented new data from a Phase Ib open-label, dose escalation trial of varlitinib in combination with modified irinotecan and infusional 5-fluorouracil chemotherapy at the 2019 European Society for Medical Oncology Congress. The OS was 13% and the median PFS was 4.2 months.

ASLAN Pharmaceuticals announced late-breaking topline data from a phase 2 study conducted in China testing varlitinib and capecitabine in second line BTC patients. Biliary tract cancer (BTC) patients treated with varlitinib plus capecitabine in second line achieved a response rate of 11% including two complete responses, median PFS of 2.7 months and OS of 5.8 months Patients on study appeared to present with more aggressive disease as only 10% of patients responded to first line gemcitabine-based treatment prior to enrolment Varlitinib plus capecitabine may provide a new therapeutic option for second line BTC patients Singapore, 19 September 2019 – ASLAN Pharmaceuticals (Nasdaq:ASLN, TPEx:6497), a clinical-stage oncology and immunology focused biopharma company, today announced late-breaking topline data from a phase 2 study conducted in China testing varlitinib and capecitabine in second line BTC patients. The data was presented during an oral session by Dr Weijia Fang, Associated Chief Physician, MD, Department of Medical Oncology, Zhejiang University, at the 2019 Chinese Society of Clinical Oncology (CSCO) meeting in Xiamen, China. The phase 2 study, which was closed before the completion of recruitment as previously announced, enrolled 62 patients in mainland China that had progressed on gemcitabine -based chemotherapy. The objective response rate in evaluable patients was 11% (including 2 patients with complete responses), the median progression free survival (PFS) was 2.7 months and overall survival (OS) was 5.8 months. 45% of patients were alive at 6 months and 35% at 12 months. Overall survival data was based on 31 events and is still maturing. The varlitinib plus capecitabine combination was well tolerated in this difficult to treat patient population. ASLAN previously reported that patients enrolled into this study appeared to have performed significantly worse, prior to recruitment, in the first line setting than observed in published global studies, suggesting that patients in China may present with more aggressive and refractory disease. Based on patient records, the response rate in first line with gemcitabine -based chemotherapy of the patients recruited in ASLAN’s study was approximately 10% with a median PFS of 3.9 months. In comparison, the ABC-02 [1] study (NEJM) that was conducted solely in the UK showed a first line response rate of 26% and PFS of 8 months for patients on gemcitabine and cisplatin . Professor Qin Shukui, Deputy Director of People’s Liberation Army 81 Hospital (Nanjing, China), commented: “ The varlitinib plus capecitabine combination was safe and well tolerated in Chinese BTC patients and could represent a new therapeutic option in this difficult to treat disease.” Dr Mark McHale, Head of R&D, ASLAN Pharmaceuticals, said: “The current prognosis of patients with advanced biliary tract cancer remains extremely poor – there are no drugs approved globally to treat this disease, so this new data with varlitinib may offer an exciting new therapeutic option. Varlitinib is a potent inhibitor of the HER family of receptors which are all highly expressed in BTC. We are very encouraged to see that the response of patients to varlitinib and capecitabine in second line is similar to their response to gemcitabine -based therapy in first line. There is also a population that show durable responses with improved overall survival.” Enrolment in a global pivotal study of varlitinib in second line BTC, the TreeTopp (TREatmEnT OPPortunity) study, was completed ahead of schedule in December 2018 and topline data is expected in the second half of 2019. ASLAN announced in January that the single-arm China study would be closed early as it would have read out – if fully recruited – after the TreeTopp study. If positive, ASLAN intends to use data from the TreeTopp study and the China study to submit a New Drug Application (NDA) in China, the US and other major geographies. A copy of the abstract, titled: “JADETREE*: A phase 2A, single arm, multicenter, study of the panHER inhibitor varlitinib plus capecitabine in Chinese patients with advanced or metastatic biliary tract cancer (BTC)” , is available on ASLAN’s website ( ). Media and IR contacts Emma Thompson Spurwing Communications Tel: +65 6571 2021 Email: ASLAN@spurwingcomms.com Robert Uhl Westwicke Partners Tel: +1 858 356 5932 Email: robert.uhl@westwicke.com About varlitinib (ASLAN001) Varlitinib (ASLAN001) is a highly potent, oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors HER1, HER2 and HER4. These receptors can be mutated or overexpressed in many tumours, which can cause excessive proliferative activity and uncontrolled growth. Therefore, by inhibiting the activation of the HER receptors, varlitinib could inhibit proliferation and control tumour growth. Varlitinib has been granted orphan drug designation in the United States for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer, and was awarded orphan drug designation for the treatment of biliary tract cancer by the Ministry of Food and Drug Safety in South Korea. About ASLAN Pharmaceuticals ASLAN Pharmaceuticals (Nasdaq:ASLN, TPEx:6497) is a clinical-stage oncology and immunology focused biopharma company targeting cancers that are both highly prevalent in Asia and orphan indications in the United States and Europe. Led by a senior management team with extensive experience in global and regional development and commercialisation, ASLAN is headquartered in Singapore and has offices in Taiwan and China. ASLAN’s clinical portfolio is comprised of three product candidates which target validated growth pathways applied to new patient segments, novel immune checkpoints and novel cancer metabolic pathways. ASLAN’s partners include Array BioPharma, Bristol-Myers Squibb, Almirall and CSL. For additional information please visit . Forward looking statements This release contains forward-looking statements. 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