Antengene's Partner, Karyopharm Therapeutics Inc., announced updated data of eltanexor for the treatment of patients with hypomethylating agent (HMA) refractory myelodysplastic syndrome (MDS) at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

This Phase I/II study evaluated single-agent eltanexor in patients with higher-risk MDS, ie, high-risk or intermediate-2 MDS by the International Prognostic Scoring System (IPSS) and 5%-19% myeloblasts. The patients enrolled in the trial were evaluated with eltanexor at the two daily doses of 10 mg (n=5) or 20 mg (n=10) for 5 days per week of a 28-day cycle.

Out of the 20 patients enrolled, 15 patients were evaluable for efficacy and constitute the population studied in this analysis. Of the 15 patients evaluable for efficacy, 7 (47%) had marrow complete response (mCR) and 5 (33%) had stable disease (SD) for a total disease control rate (DCR, mCR+SD) of 80% (60% for all patients' analysis). In the 10 mg cohort (n=5), all patients derived clinical benefit with 3 patients (60%) reaching mCR and 2 patients (40%) reaching SD. In the 20 mg cohort (n=10), 4 patients (40%) had mCR and 3 (30%) had SD. Four patients had hematologic improvement (HI) and became transfusion-independent for at least 8 weeks including 2 patients with tri-lineage HI. The overall survival (OS) for patients who reached mCR (n=7) was significantly longer than that for patients who did not reach mCR (n=8): median 11.86 vs 8.67 months (hazard ratio [HR]=0.27, p=0.05), and significantly longer than the OS for patients with progression disease (PD, n=3, mOS=3.15 mo, HR=0.23, p=0.04). Patients with disease control (n=12) had numerically longer median overall survival (mOS) than patients with PD (9.86 vs 3.15 mo, HR=0.38, p=0.09). Patients with HI had a mOS of 10.58 months.

Patients with MDS refractory to HMAs have limited therapeutic options and a dismal prognosis with a median overall survival (mOS) of 4-6 months. Eltanexor is a next-generation, oral XPO1 inhibitor that showed anti-tumor activity and lower central nervous system penetration compared to selinexor, the first-in-class XPO1 inhibitor, in nonclinical models. It was hypothesized that eltanexor could be dosed more frequently than selinexor with a lower incidence of centrally mediated nausea.

Antengene has entered into a strategic collaboration with Karyopharm, through which it obtained the rights to develop and commercialize four drug candidates including eltanexor in 17 Asia Pacific markets. Antengene is currently conducting clinical trials of eltanexor in patients with MDS or advanced solid tumors in China. Of these, the Phase I/II trial of eltanexor for the treatment of MDS (the HATCH trial) has already dosed its first patient.

About Eltanexor (ATG-016)

Eltanexor is a next-generation selective inhibitor of nuclear export (SINE) compound. In preclinical models, compared to the first-generation SINE compound, eltanexor demonstrated 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.

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.