Antengene Announces First Patient Dosed in Phase I/II Trial of Eltanexor for the Treatment of Myelodysplastic Syndrome

Antengene Corporation Limited, a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, today announced the dosing of the first patient in China in a Phase I/II trial (the HATCH trial) of eltanexor (ATG-016), a next-generation selective inhibitor of nuclear export (SINE) compound, for the treatment of intermediate and higher-risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System (IPSS-R) after failed treatment with hypomethylating agent (HMA) based therapies. This single-arm, open-label clinical trial is designed to evaluate the safety and efficacy of eltanexor monotherapy in the prespecified patients with MDS.

MDS is a malignancy originated in the bone marrow hemopoietic stem-cells of which the incidence increases significantly with age. The median overall survivals (OS) of patients with intermediate, high, and very high-risk MDS are 3, 1.6, and 0.8 years, respectively, and patients at these risk levels have a high probability of progressing to acute myeloid leukemia (AML). HMAs including azacytidine and decitabine are standard of care treatments for MDS. However, HMAs do not eradicate neoplastic clones and only generate response in around 50% of patients with MDS. Patients with MDS refractory to HMA-based therapies have a poor prognosis, limited options for follow-up treatment, and a median OS of only about four to six months.

Eltanexor is a next-generation SINE compound, and an antagonist of the nuclear export protein XPO1, of which expression correlates with a poor prognosis and resistance to chemotherapies. Eltanexor induces apoptosis in tumor cells by inhibiting XPO1 and has demonstrated favorable anticancer activity in xenograft models of hematological malignancies and solid tumors.

Data from a Phase I/II clinical study of eltanexor in patients with higher-risk MDS refractory to HMAs, as presented at the 2019 American Society of Hematology (ASH) Annual Meeting, have demonstrated an objective response rate (ORR) of 35%, with bone marrow complete response (mCR) achieved by all of those patients assessed as ORR. Meanwhile, these clinical results of eltanexor also showed a favorable safety and tolerability profile. In addition to MDS, eltanexor is also being investigated for the treatment of advanced solid tumors in China.

"We are encouraged by the dosing of the first MDS patient in the HATCH trial, as it marks the beginning of the clinical development of our second SINE compound," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "Eltanexor was found to be safe and well tolerated in preclinical studies and showed potent anti-cancer activity in xenograft models, and demonstrated preliminary clinical efficacy and well tolerated safety profile in patients with high risk MDS. We are eager to explore the therapeutic potential of eltanexor and to continue working with regulators as we advance this clinical program with the goal of benefiting patients with intermediate and higher-risk MDS in China."

About Eltanexor (ATG-016)

Eltanexor is a next-generation selective inhibitor of nuclear export (SINE) compound. Compared to the first-generation SINE compound, eltanexor has lower blood-brain barrier penetration and broader therapeutic window which allows more frequent dosing and a longer period of exposure at higher levels with better tolerability. Therefore, eltanexor may be used to target a broader range of indications. Antengene is currently conducting clinical trials of eltanexor in patients with myelodysplastic syndrome (MDS) or advanced solid tumors in China.

About Antengene

Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage R&D driven biopharmaceutical company focused on innovative medicines for oncology and other life-threatening diseases. Antengene aims to provide the most advanced anti-cancer drugs to patients in the Asia Pacific Region and around the world. Since its establishment in 2017, Antengene has built a broad and expanding pipeline of clinical and pre-clinical stage assets through partnerships as well as in-house drug discovery, and obtained 15 investigational new drug (IND) approvals and submitted 5 new drug applications (NDA) in multiple markets in Asia Pacific. Antengene's vision is to "Treat Patients Beyond Borders". Antengene is focused on and committed to addressing significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.