Cell apoptosis and checkpoint suppression! Asain Pharma has partnered with Mercado to develop MDM2-p53 inhibitor APG-115/Keytruda for the treatment of solid tumors!

, July 06, 2020 /
BiovalleyBIOON/ Ascent Pharma is a China-based, global-oriented research and development of original new drug products in the clinical stage, dedicated to the development of innovative drugs in the treatment ofcancer, hepatitis B and aging-related diseasesRecently, the company announced a clinical partnership with Merck and Co to evaluate its MDM2-
p53inhibitor APG-115 and Mercado's anti-PD-1 therapy Keytruda (Corrida, generic name: pemzumabrob, Pabolizumab) to treat patients with advanced solid tumorsunder the agreement, AXA Pharma will sponsor an open-label, multi-center, Ib/II study (NCT03611868) to assess the efficacy and safety of APG-115 and Keytruda's joint treatment of multiple solid tumors, such as non-small cell lung cancer (NSCL)C),melanoma, urinary skin cancer, fatty sarcoma, malignant peripheral neuropaltumor (MPNST), and anti-PD-1/PD-L1 therapy to treat drug-resistant or relapsed, or have not received such medication at at-type at-type at-typetumorPhase II of the study has been initiated and is expected to enroll 80 patients in several clinical centers in the United StatesAsain Pharma and Mercado will share information on the study through a joint development committeethe essence of all human cancers is to impair the anti-cancer function of p53In about half of human cancers, the gene TP53, which encodes the p53 protein, mutates or is missing, which inactivates p53's anti-cancer functionOf the remaining 50% of cancers, p53 remains wild However, MDM2 proteins effectively inhibit their p53 function through the protein-protein interaction of the formulation It is a promising tumor treatment strategy to restore the anti-cancer function of p53 by inhibiting the interaction of p53 with MDM2 APG-115 is an oral bioavailable, highly selective small molecule MDM2-p53 inhibitor with a high binding affinity for MDM2 (IC50 and Ki values are 3.8nM and 1nM, respectively), which can restore the anti-cancer function of p53 by blocking MDM2-p53 interactions APG-115 induces cell cycle blocking and apoptosis in a p53-dependent manner preclinical studies have also shown that APG-115 can promote the production of cat-inflammatory cytokines in T cells, enhance the activation of CD4-T cells, and increase the expression of PD-L1 in a variety of tumor cells After combining APG-115 with PD-1 inhibitors, enhanced antitumor activity was shown in a variety of tumor models The results of the trial Ib were recently presented at ASCO 2020, confirming good tolerance of APG-115 and Keytruda combination drugs and showing encouraging anti-
tumor effects in several tumor types data showed that of the 18 assessable patients, one received full remission (CR) for up to 20 months, 2 received partial remission (PR) for 8-9 months, and 7 obtained disease stabilization (SD) for 1.5-7 months The objective mitigation rate (ORR) was 16.7% and the disease control rate (DCR) was 55.5% In addition, pharmacokinetics (PK) analysis showed that aUC and Cmax of APG-115 increased with dose increases in the 50-200 mg dose range, and a combination of APG-115 and Keytruda did not affect the PK parameters of APG-115 "We are pleased to have a clinical partnership with The Saxo, the global leader in the medical industry," said Dr Dajun Yang, Chairman and Ceo of AxaPharmaceutical APG-115 is a key candidate in the pipeline of apoptosis of Axapharmaceuticals, and has great potential in the treatment of advanced solid tumors Based on promising Phase Ib trial data, we look forward to working closely with Mercado to further study a combination of APG-115 and Keytruda to provide more effective treatment options for patients with advanced solid tumors "
Keytruda is a PD-(L) 1 tumor immunotherapy that helps detect and fight tumor cells by improving the body's immune system." Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, activating T lymphocytes that may affect tumor cells and healthy cells So far, 11 PD-(L) 1 oncology immunotherapy have been approved worldwide, of which Keytruda is the leader in the field, with more than 20 therapeutic indications approved and global sales reaching $11.1 billion in 2019, up 58% from the previous year Mercado has the largest clinical development of immunothologists in the industry, with more than 1,200 clinical trials
investigating Keytruda's role in a variety of types of tumor and therapeutic context The Keytruda Clinical Project aims to understand the drug's role in cancer and factors that may predict patients' benefits from Keytruda treatment, including exploring several different biomarker (BioValleyBioon.com) original origins: 1, Ascentage Pharma Announces Clinical Video Trial Agreement with MSD to Evaluate APG-115 in Combination With Key TruDA ® (pembrolizumab) in Advanced Solid S Tumors 2, APG-115
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