Our lead candidate AN2025, is a pan-PI3K inhibitor currently undergoing a global Phase III trial. In-licensed from Novartis, we have the exclusive global rights to develop and commercialize AN2025. It is currently the most advanced drug candidate in registrational clinical trial phase for the treatment of recurrent or metastatic HNSCC after disease progression with anti-PD-1/PD-L1 therapy. We believe that AN2025, if approved, has the potential to be the first global product with a label to address this unmet medical need and capture a sizable addressable market. In April 2023, the Company entered into an option agreement with Nippon Kayaku to further advance the commercialization of this candidate in Japan.

AN2025 BURAN Phase 3 Trial in r/m HNSCC After Anti-PD-1/PD-L1 treatment 

(NCT04338399)

The BURAN study is a randomized, open-label Phase 3 study assessing the treatment effect of once-daily AN2025 in combination with weekly paclitaxel compared to weekly paclitaxel alone in patients with r/m HNSCC that have progressed after:

Ÿ   Prior anti-PD-L1 monotherapy;

Ÿ   Prior anti-PD-L1 therapy in combination with platinum-based therapy; or after

Ÿ   Sequential treatment of anti-PD-L1 therapy, either prior to or post platinum-based therapy

In November 2023, we announced the completion of patient enrollment in the phase III clinical trial at more than 180 sites around the world, spanning 18 markets in North America, Europe, Asia, and South America. Enrolled patients are randomized in a 2:1 ratio to receive either daily AN2025 (100 mg) in combination with weekly paclitaxel (80 mg/m2) or weekly paclitaxel alone in a 21-day treatment cycle. The primary endpoint of this study is OS for the entire (intent-to-treat) population of patients. Secondary endpoints include safety profile and other efficacy measurements such as PFS, ORR, DoR, and HRQoL.

BERIL-1 Phase 2 Study for r/m HNSCC(NCT01852292)^1,2

The trial was a multi-center, randomized, double-blind, placebo-controlled Phase II study assessing patients with histologically or cytologically-confirmed recurrent or metastatic HNSCC after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. A total of 158 eligible patients were enrolled from 58 centers across 18 jurisdictions and randomly assigned (1:1) to receive second-line oral AN2025 (n=79, 76 treated with 100 mg once daily) or placebo (n=79, 78 treated with 80 mg/m2 on days 1, 8, 15 and 22) plus intravenous paclitaxel in 28-day treatment cycles.

The clinical data showed that the combination of AN2025 with paclitaxel achieved an mOS of over 10 months (vs. 6.5 months in the placebo plus paclitaxel group), an mPFS of 4.6 months (vs. 3.5 months in the placebo plus paclitaxel group), and a 39.2%ORR (vs. 13.9% in the placebo plus paclitaxel group). These data also showed that when AN2025 was combined with paclitaxel, grade 3-4 adverse events (“AEs”) (82% in the AN2025 plus paclitaxel group vs. 72% in the placebo group), serious adverse events (“SAEs”) (57% in the AN2025 plus paclitaxel group vs. 47% in the placebo group) or on-treatment deaths (20% in the AN2025 plus paclitaxel group vs. 22% in the placebo group) is comparable to paclitaxel alone.

Based on the clinical results, we received Fast Track designation from the FDA for the investigation of AN2025 in recurrent or metastatic HNSCC with disease progression on or after platinum-based therapy.

Phase 1 study of Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (NCT04975958)

To fully explore the potential of AN2025 and AN0025, we initiated a study of the triple combination of AN2025, AN0025 and atezolizumab, an anti-PD-L1 antibody. This study exemplifies our strategy to achieve synergistic effects from combining targeted therapy and immunotherapy. AN2025 targets not only PI3K mediated tumorigenesis (e.g., via inhibition of PI3Kα / PIK3CA mutants) but also the immunosuppression of the tumor microenvironment (e.g., via inhibition of PI3Kδ and PI3Kγ). Leveraging the complementary and synergistic antitumor effects of our drug candidates in combination therapies, AN2025 is designed to mechanistically complement and synergize with the combination of anti-PD-1/PD-L1 antibody and AN0025 to form an improved treatment regimen for patients with multiple advanced solid tumors.In different tumor-bearing mouse models, we have consistently observed significant antitumor activity in the triple combination of AN2025, AN0025 and atezolizumab compared with the dual or double combination therapy.

In July 2021, we initiated a Phase I clinical trial to evaluate the triple combination of AN2025, AN0025, and atezolizumab, for a variety of PIK3CA mutant solid tumors. The trial is a Phase Ia, multi-center, open-label clinical trial study in patients with locally advanced or metastatic cancer that were previously treated with one to four lines of therapy. This trial is conducted in the U.S. It consists of three DLT observations I, II, and III. Observations I (AN2025+atezolizumab) and II (AN0025+atezolizumab) are double combination treatments, which were completed in September 2022. Observation III (AN2025 + AN0025 + atezolizumab) is currently underway after a thorough review of the safety data from observations I and II.

Reference

1.Lancet Oncol,2017,323-335(pdf).

2.Clin Cancer Res,2018,2025-2516(pdf).