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ASLAN Pharmaceuticals – ASLAN001 (ARRY-543) – HER2 / EGFR Program
In July 2011, we entered into a Collaboration and License Agreement with ASLAN Pharmaceuticals to develop Array's HER2 / EGFR inhibitor, ASLAN001 (ARRY-543), which is currently in Phase 2 development in patients with gastric cancer in Asia. ASLAN001 is a novel, selective and oral HER2 / EGFR inhibitor, and has shown clinical activity in both HER2-positive and EGFR-positive tumors. Under the agreement, ASLAN is funding and developing ASLAN001 through clinical proof-of-concept. Upon achievement of proof-of-concept, ASLAN will identify a global partner for Phase 3 development and commercialization. Array will share a significant portion of the proceeds of such partnering transaction.

The agreement with ASLAN will remain in effect for two years after conclusion of the initial development plan, unless ASLAN has entered into a license agreement with a third party for the further development and commercialization of the program, in which case the agreement shall remain in force and effect. Either party may terminate the agreement prior to expiration of the term following breach of the agreement by the other party. ASLAN is responsible for diligently advancing development of ASLAN001 under an agreed-upon development plan.

Gastric cancer is a major public health problem in East Asia. Patients with locally advanced, metastatic or recurrent disease have a poor prognosis, with an overall median survival of approximately 11 months. EGFR and HER2 receptors are commonly overexpressed together in gastric cancer. Data from pivotal studies of Herceptin® (trastuzumab), indicate that the activity of this drug is limited to the subset of patients whose disease has amplified copies of the HER2 gene. We believe ASLAN001 has the potential to augment or supersede the activity of Herceptin in this population, and in the broader population of gastric cancers that co-express both EGFR and HER2 receptors.

In a Phase 1 trial, ASLAN001 produced prolonged stable disease in patients with solid tumors who had previously failed prior treatments. Tablets of ASLAN001 were well tolerated up to 500 mg twice daily dosing. Systemic concentrations of ASLAN001 increased with escalating doses at all dose levels tested. Sixty percent of patients receiving doses of 200 mg twice daily and higher had prolonged stable disease.

In a Phase 1 expansion cohort in patients with HER2-positive metastatic breast cancer or other ErbB-family cancer, ASLAN001 was generally well tolerated and demonstrated evidence of tumor regression and prolonged stable disease in EGFR- and HER2-expressing cancers. Twenty-one metastatic breast cancer patients were evaluated: of the 12 with available biopsies, eight were confirmed HER2-positive. Of the confirmed patients with HER2-positive metastatic breast cancer in this study, 63% had stable disease. Clinical benefit (measured by tumor regression or stable disease) was demonstrated in five of the eight confirmed HER2 patients and patients with confirmed co-expression of HER2 and EGFR tended to have the best clinical benefit. In a cohort of patients with other cancers shown to over-express HER2 and EGFR, a patient with cholangiocarcinoma experienced a tumor marker response that was accompanied by a 25% regression of target lesions.

In a Phase 2 clinical trial in patients with gastric cancer, ASLAN001 reduced cell proliferation and cell survival in gastric tumors that were either coexpressing EGFR and HER2 or that were HER2 amplified. This is the first time a drug has shown activity in this patient population. The burden of gastric cancer is particularly severe in Asia. It is the most prevalent cancer in males in China, where it is estimated to affect over half a million people. The Phase 2, open-label, multi-center study was conducted in South Korea, and was designed to evaluate the biological activity of ASLAN001 in patients with recurrent/metastatic gastric carcinoma whose tumors were HER2 amplified or coexpressing EGFR and HER2. Twenty-three patients, who had previously failed on one or more rounds of chemotherapy and, where eligible, trastuzumab, each received 500mg of ASLAN001 orally twice daily as monotherapy for 28 days. In this heavily pretreated population, ASLAN001 led to a downregulation of signaling pathways responsible for cell proliferation, and a reduction in cell survival and cell proliferation. Toxicities observed were consistent with other drugs in this class and the previously reported profile of this compound.

Development Status: During fiscal 2013, ASLAN reported positive results for a Phase 2a clinical trial with ASLAN001 in Asia in patients with gastric cancer and intends to begin a randomized Phase 2b study in gastric cancer and is exploring the use of ASLAN001 in other indications.

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