Targeting the Bcl-2 Pathway

 

APG-2575

Bcl-2 selective inhibitor
(Granted ODD)

Indications: leukemia, waldenström macroglobulinemia (WM) and other blood cancers

APG-2575 is a novel, orally administered Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat a variety of hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells.

Ascentage Pharma has previously commenced Phase I studies of AGP-2575 single agent in China, Australia, and the United States. Since March 2020, the company has received approvals and clearances for several Phase Ib/II studies of APG-2575 in China, Australia, and the US, and is advancing clinical development of APG-2575 for a variety of hematologic malignancy indications, including relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, WM, relapsed/refractory multiple myeloma, and relapsed/refractory acute myeloid leukemia.

 

 

 

APG-2575
 

APG-1252

Bcl-2/xL inhibitor

Indications: small cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), lymphoma, and other solid tumors

APG-1252 is a novel, highly potent, small-molecule drug that was discovered and is being developed by Ascentage Pharma. APG-1252 is designed to treat SCLC, NSCLC, lymphoma, and other solid tumors by selectively blocking Bcl-2 and Bcl-xL to restore the apoptosis process.

Two Phase I dose-escalation trials in patients with advanced cancers are currently ongoing in the U.S. and Australia, and a Phase I dose-escalation/expansion trial as monotherapy in patients with SCLC is ongoing in China.

 

 

 

APG-1252
 

AT-101

Bcl-2/Bcl-xL/Mcl-1 inhibitor

Indications: chronic lymphocytic leukemia

AT-101 is a pan-Bcl-2 inhibitor we are developing for CLL and MM that blocks Bcl-2, Bcl-xL, Bcl-w and Mcl-1 proteins. Since 2005, 14 Phase I and II clinical trials for AT-101 have been conducted among more than 700 patients with solid tumors or blood cancers. Chinese patients were also enrolled in a multinational, multicenter, randomized, double-blinded Phase II trial in non-small cell lung cancer. Results from these trials show that AT-101 is well tolerated. AT-101, either as a single agent or in combinations, has shown anti-tumor activity in CLL or hormone refractory prostate cancer. We are currently conducting a Phase II trials for AT-101 in combination with lenalidomide or rituximab in patients with relapsed/refractory CLL, or r/r CLL, in China. Additionally, we are coordinating an investigator-initiated Phase I/II trial in the United States to investigate the efficacy and safety of AT-101 in patients with r/r CLL or relapsed/refractory multiple myeloma, or r/r MM.

 

 

 

 

Targeting the IAP Pathway

 

APG-1387

IAP antagonist

Indications: Hepatitis B, advanced pancreatic cancer and other solid tumors

APG-1387 is a novel small molecule IAP (Inhibitor of Apoptosis Protein) antagonist, that was discovered and is being developed by Ascentage Pharma. APG-1387 degrades IAPs by mimicking endogenous SMAC molecule to induce programmed cell death or apoptosis.

Ascentage Pharma is developing APG-1387 globally, and has completed Phase I dose-escalation trials in patients with solid tumors in China and Australia, and a Phase Ib/II clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the US. In addition, APG-1387 is also being investigated in a Phase Ib trial for the treatment of patients with Chronic Hepatitis B (CHB) in China. In February 2020, Ascentage Pharma was cleared to initiate a Phase Ib/II study of APG-1387 in combination with nab-paclitaxel plus gemcitabine for the treatment of advanced pancreatic cancer. In April 2020, the company received clearance for a Phase II study of APG-1387 in combination with entecavir for the treatment of CHB.

 

 

 

APG-1387
 

Targeting the MDM2-p53 Pathway

 

APG-115

MDM2-p53 inhibitor

Indications: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), salivary gland cancer and other solid tumors

APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI.

Ascentage Pharma has previously commenced three clinical trials of APG-115 in the US, including a Phase I study as single agent, a Phase Ib/II study in combination with pembrolizumab for treatment of metastatic melanoma and other advanced solid tumors, and a Phase I/II study as a single agent or in combination with chemotherapy for treatment of salivary gland cancer. APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China. A Phase I study as a single agent, and a Phase Ib study as a single agent or in combination with chemotherapy for treatment of AML or MDS are ongoing in China.

 

 

APG-115