Ascentage Pharma's MDM2-p53 Inhibitor Alrizomadlin (APG-115) Granted Fast Track Designation by the US FDA for the Treatment of Relapsed/Refractory Unresectable or Metastatic Melanoma

SUZHOU,China,and ROCKVILLE,MD,Sept 23,2021 --Ascentage Pharma (6855.HK),a global biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today announced that its novel MDM2-p53 inhibitor alrizomadlin (APG-115) has been granted a Fast Track Designation (FTD) by the US Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma,relapsed/refractory to prior immuno-oncologic agent (IO) treatments. Previously,alrizomadlin was already granted five Orphan Drug Designations (ODDs) by the US FDA,one of which was for the treatment of stage IIB-IV melanoma.

Melanoma is a potentially deadly dermatologic malignancy that has been increasingly prevalent globally. The current lifetime risk of developing melanoma is 1 in 63 in the US1. In 2019,an estimated 96,480 patients have been diagnosed with melanoma and about 7,230 patients with melanoma have died in the United States2. Advanced melanoma presents an enormous clinical challenge as it is prone to metastasis and lacks survival benefit from chemotherapies. Immune checkpoint inhibitors (ICIs) are currently recommended for the first-line treatment of most patients with metastasized melanoma3. Although approximately 35% to 60% of the patients have a response evaluation criterion in solid tumors (RECIST) response to ICIs,the remaining 40% to 65% have shown minimal or no RECIST response at the outset,and 43% of the responders develop acquired resistance in the three years after receiving ICIs4. Therefore,patients who failed on or developed acquired resistance to ICIs are in urgent need of new treatment options.

This FTD for alrizomadlin is based on combined preclinical results and preliminary clinical data from an ongoing Phase II study (APG-115-US-002,Clinicaltrials.gov Identifier: NCT03611868). The preliminary clinical data released in an oral report at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting showed that alrizomadlin has favorable antitumor activity and a manageable safety profile. The cohort of patients with PD-1/PD-L1 inhibitor-resistant melanoma treated with alrizomadlin in combination with pembrolizumab achieved one case of complete response (CR),an objective response rate (ORR) of 24.1%,and a disease control rate (DCR) of 55.2%.

The FTD expedites the development and review of drug candidates to treat serious diseases/conditions that present urgent unmet clinical needs. This FTD for alrizomadlin will lead to a series of benefits that could accelerate the clinical development and review for this drug candidate,including more frequent communications and meetings with the FDA during its clinical development; and if the FDA determines appropriate,to be allowed to enter Rolling Review,a process that allows a company to submit New Drug Applications (NDAs) by sections,rather than waiting until all required materials become available. This FTD also paves the way for alrizomadlin to potentially obtain Accelerated Approval and Priority Review designations in the future.

"Alrizomadlin is a key drug candidate in Ascentage Pharma's apoptosis-targeting pipeline. An ODD and a FTDhave already been granted to alrizomadlin by the US FDA for the treatment of melanoma,signifying the enormous therapeutic potential of the asset," said Dr. Dajun Yang,Chairman & CEO of Ascentage Pharma. "This FTD will help strengthen our communications with the US FDA in the clinical development of alrizomadlin,speed up the clinical development of alrizomadlin in the US and globally,thus potentially accelerating the drug candidate towards NDA submissions. We will move forward in full speed with the clinical development of alrizomadlin in the hope of offering a new treatment option to patients with melanoma."

References

1. Stephanie C,Christy S,Jessica W. Epidemiology and Risk Factors of Melanoma. Surg Clin North Am. 2020 Feb;100(1):1-12.

2. Cancer Facts & Figures 2019. American Cancer Society. Link: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html

3. National Comprehensive Cancer Network (NCCN®) Guidelines for the Treatment of Cancers,Version 2.2021

4. Tuba G,James W,Richard S,et al. Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma. Clin Cancer Res. 2018 Mar 15;24(6):1260-1270.

About APG-115 (alrizomadlin)

Being developed by Ascentage Pharma,alrizomadlin is an orally administered,selective,small-molecule inhibitor of the MDM2 protein. Alrizomadlin has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 protein-protein interaction. Alrizomadlin is the first MDM2-p53 inhibitor entering clinical development in China and is currently being investigated in multiple Phase Ib/II studies in solid tumors and hematologic malignancies in China,Australia,and the US. To date,alrizomadlin has been granted a total of five Orphan Drug Designations (ODDs) by the US FDA for the treatment of gastric cancer,acute myeloid leukemia,soft tissue sarcoma,retinoblastoma,and stage IIB-IV melanoma.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B,and age-related diseases. On October 28,2019,Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 6855.HK.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis,or programmed cell death. The company has built a pipeline of eight clinical drug candidates,including novel,highly potent Bcl-2,and dual Bcl-2/Bcl-xL inhibitors,as well as candidates aimed at IAP and MDM2-p53 pathways,and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials in the US,Europe,and China. Ascentage Pharma has been designated for multiple Major National R&D Projects,including five Major New Drug Projects,one New Drug Incubator status,four Innovative Drug Programs,and one Major Project for the Prevention and Treatment of Infectious Diseases. HQP1351,the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML),has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA. A New Drug Application (NDA) for HQP1351 has been submitted and subsequently granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) in China. To date,Ascentage Pharma has obtained a total of 12 ODDs from the US FDA for 4 of the company's investigational drug candidates.

Leveraging its robust R&D capabilities,Ascentage Pharma has built a portfolio of global intellectual property rights,and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology,MD Anderson Cancer Center,Mayo Clinic,Dana-Farber Cancer Institute,MSD,and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs,and is setting up its world-class commercial manufacturing and Sales & Marketing teams. Ascentage Pharma aims to continuously strengthen its R&D capabilities and accelerate its clinical development programs to fulfil its mission of 'addressing unmet clinical needs in China and around the world' for the benefit of more patients.

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