Asia-Sheng Pharmaceuticals Announces Latest Clinical Data on New Drugs for Apoptosis Series

APG-115APG-115 is an oral bio-available, highly selective small molecule MDM2 inhibitor developed by AXA PharmaceuticalsAPG-115 has a high affinity for MDM2, which restores p53 tumor inhibition by blocking MDM2-p53 interactionsAPG-115 is the first MDM2-p53 inhibitor to enter clinical phase in ChinaAxa Pharma presented two findings of a PG-115 at the ASCO2020 conference1APG-115 in conjunction with Paboli-Zhuzumab treatment for advanced metastatic solid tumorsAxa Pharma conducted an open label, multicenter, Ib/II phase study in the United States to assess the safety, tolerance, pharmacokinetics (PK), pharmacology (PD) and antitumor activity of Patients with APG-115 Combined Paboli ZumaAt present, the Ib dose increase study has been completed and Phase II is under wayAs of April 1, 2020, a total of 19 patients in the Ib phase study received APG-115 combined Paboli zuma therapyAPG-115 has 4 dose groups of 50 mg, 100 mg, 150 mg and 200 mg, and no dose-restricted toxicity was found and the maximum tolerable dose (MTD) was not reachedBased on safety data, the recommended dose of APG-115 and Paboli Zuma monitamcines was determined to be 150 mg every 2 daysAPG-115 and Paboli Bead Singa-resistant are generally well toleratedThe most common adverse drug-related reactions (TRAEs) (-10%) include: nausea, vomiting, fatigue, decreased platelet count, reduced neutrophil count, decreased appetite, diarrhea and hypothyroidismof 18 patients whose efficacy was assessable, 1 received full remission (CR) for up to 20 months (is still under treatment), 2 received 8-9 months of partial remission (PR) (1 patient with non-small cell lung cancer with failure of 3 months of navuzumast treatment, 1 patient with appendicadenum cancer without tumor immunotherapy), and 7 cases reached 1.5-7 months of disease stabilization (SD)The objective mitigation rate (ORR) was 16.7% and the disease control rate (DCR) was 55.5%in general, the clinical data of Phase Ib safe and effective are promising for the joint use of APG-115 and Paboli Zuma Phase II clinical trials are currently under way for cancer patients with specific biomarkers 2 APG-115 Treatment of Advanced Fatty Sarma and Other Solid Tumors Asheng Pharmaceuticals conducted a Phase I study in China to treat advanced fatty sarcoma and other solid tumors As of January 9, 2020, 21 eligible patients with advanced solid tumors received APG-115 treatment at 3 dose levels (100 mg, 150 mg, and 200 mg) Fat sarcoma account for two-thirds of all tumors Most of the 21 patients completed at least 2 cycles of APG-115 treatment, and 1 patient completed 6 cycles of APG-115 treatment evaluated the efficacy of 19 patients (4 patients still under treatment), of which 13 were liposarcoma Of these patients, 1 PR, 12 SDcases, ORR was 5.3% and DCR was 68.4% The ORR was as high as 11.1% in patients with wild TP53 fat sarcoma and 77.8% of DCR TraEs occur during common treatment including anemia and decreased count of white blood cells and platelets However, most AEs are Level 1 or 2 and the incidence of adverse events in the 100 mg dose group is low current research has found that APG-115 is given once the next day, 21 days of continuous administration of the drug 7 days of the drug regimen, the overall safety and tolerance is good, especially at the 100 mg dose level, APG-115 RP2D is 100mg daily administration in general, APG-115 single drug saw clinical efficacy in patients with fatty sarcoma and patients expressing TP53 wild tumors, and this result also supported the predictive efficacy of APG-115 in fatty sarcoma and other tumors The continuous remission observed after discontinuation of the drug in 1 PR patient for more than 10 months suggests that APG-115 may have host immunomodulation effect and provides impetus for further evaluation of APG-115 single drug therapy or combination with immunotherapy Professor Zhang Xing, Chief Physician of Melanoma and Sarcoma At Sun Yat-sen University Cancer Hospital, , said: "Late fat sarcoma is a common histological type in malignant soft tissue sarcoma, with poor prognosis and high recurrence rate, and there is a lack of effective treatment at this stage." APG-115 is an effective MDM2-p53 inhibitor, and last year ASCO reported impressive data on liposarcoma In the updated data, we performed a safety amplification in the 100 mg dose group and determined its recommended dose for Phase II At the same time, previous findings have been further verified that TP53 wild type is a predictive biomarker of APG-115, and liposarcoma may be one of its potential target tumors We also look forward to more clinical studies and molecular biology evidence "
APG-1387 APG-1387 is a new type of small molecular apoptosis protein inhibitor (IAP) that AXA Pharmaceuticals has developed AXA is developing APG-1387 worldwide and has completed clinical phase I dose climbing trials for solid tumors in China and Australia, and is conducting Ib/II clinical trials in the United States for combination therapy with Paboli zumas A Phase Ib clinical trial for the treatment of hepatitis B is also under way in China, and a Phase Ib/II clinical trial for the treatment of advanced pancreatic cancer with combined chemotherapy was launched in February this year presented at the ASCO2020 conference as the result slate of the APG-1387 open label for the treatment of advanced solid tumors, phase Ib in the I/Ib study Phase I of the study was APG-1387 monodrug therapy, phase Ib phase was APG-1387 and Paboli zumas combined therapy Previous phase I clinical studies have shown that the maximum tolerable dose (MTD) of APG-1387 monodrug therapy is 45 mg per weekly intravenous drip, and DLTs include elevated lipase and facial nerve disorders The asco 2020 conference was presented with safety, tolerance and initial efficacy data in patients with APG-1387 joint Paboli Zuma anti-late-stage solid tumor As of April 1, 2020, a total of 41 patients with various advanced solid tumors received combination therapy aPG-1387 and Paboli zuma, including 10 patients with increasing doses (4 cases of 20 mg, 3 30mg, 3 cases of 45mg) and 31 patients in the MTD dose 45mg extended study results showed that aPG-1387 combined with Paboli Zuma was well tolerated and adverse events were controlled The most common TRAE (-10%) is fatigue, headache, nausea and plaque papules Facial nerve disorder was also found in only 2 patients (4.9 percent) and was not higher than in the single drug study 4 of the 37 patients whose efficacy was evaluated received PR, including 2 non-small cell lung cancer, 1 colorectal cancer, 1 breast cancer, and 12 patients with SD The overall ORR was 10.8% and the DCR was 43.2% NSCLC queues reached 50% ORR and 100% DCR; preliminary PK data from APG-1387 show that exposure (Cmax and AUC) is proportional to the dose in the dose range of 20-45 mg Preliminary PD data show that APG-1387 induces a rapid and significant cIAP-1 / XIAP inhibitory effect with potential pharmacodynamic effects in general, validity and safety data indicate that aPG-1387 combined with Paboli zuma supreatovicis is a promising anti-tumor method that deserves further study in patients with late-stage NSCLC and CRC Dr Drew W Rasco, Associate Director of Clinical Research at the San Antonio Cancer Treatment Center, , said: "The phase Ib study of the new IAP antagonists APG-1387 and Pabolizumab combined therapy has shown that the combination therapy is safe and controllable for adverse events, which is an important milestone in supporting further research in APG-1387 In addition, we have observed some exciting clinical responses that deserve further assessment in specific patient populations, including microsatellite-stabilized colorectal cancer and non-small cell lung cancer "
APG-1252 APG-1252 is a Bcl-2/Bcl-xL dual-target inhibitor class developed by AXA Pharmaceuticals, which can restore apoptosis by selectively inhibiting Bcl-2 and Bcl-xL proteins, and is clinically intended for the treatment of solid tumors such as small cell lung cancer (SCLC), lymphoma, etc Two phase I dose-increasing trials for the treatment of advanced cancer patients are currently being conducted in the United States and Australia, and a Phase I dose increase/expansion trial for sCLC as a single drug is being conducted in China 's announcement at the ASCO2020 conference is the first human trial of a metastatic solid tumor in the United States for a pED-1252( palcitoclax The purpose of this study was to evaluate the safety/tolerance, pharmacodynamics, and initial antitumor activity of APG-1252 against metastatic small cell lung cancer or other malignant solid tumors The trial was subjected to a standard "3-3" design for dose increments Take intravenous administration (30 minutes) twice a week or once, 28 days for one cycle When MTD/RP2D is determined, more patients will be included in the dose amplification phase As of December 21, 2019, a total of 42 patients participated in 8 dose groups (10mg-400mg) of APG-1252 (31 patients in the drug group twice a week and 11 in the weekly group), and the dose increment phase was completed A total of 4 cases of DLTs were observed in , all of which were level 4 platelet slower, occurring at 320 mg and 400 mg The reduction of platelets is a target toxicity reaction of APG-1252 (palcitoclax), whose countdrops rapidly after administration and quickly returns to normal without medical intervention within 2-6 days in 36 patients who were able to assess the efficacy, a total of 3 patients with small cell lung cancer, prostate cancer with low differentiation neuroendocrine tumor, and highly malignant plasma ovarian cancer achieved PR, of which THE PR of patients with small cell lung cancer lasted more than 18 drug cycles Another 7 patients achieved SD efficacy, of which 2 patients sD lasted more than 6 cycles, and 3 patients sEd efficacy was maintained for more than 4 cycles The remaining 26 patients progressed with disease progression, with an overall DCR of 27.77 percent The most common side effects of are primary or secondary 26.2% of patients had three or more TRAEs The most common TRAEs were decreased platelet count (14.3%), increased calorine transaminase (9.5%) and glutamate transaminase (7.1%) APG-1252 is well tolerated in a dose of 240 mg The 240mg weekly drug was identified as MTD and RP2D At present, the extended trial of MTD is in progress and all patients have been enrolled in the group APG-1252 exhibits linear pharmacokinetics in the 10-400 mg dose range and is proportional to the dose in general, APG-1252 showed sustainable anti-tumor effects in Phase I trials, while having the advantage of platelet safety This result supports the further development of joint APG-1252 and other treatments in the application of malignant solid tumors and blood diseases "Palcitoclax (APG-1252) is an effective new Bcl-2 family protein inhibitor that induces apoptosis of tumor cells," said Dr Nehal Lakhani, Director of Clinical Research at start Center for Cancer Care Midwest Cancer Center in the United States, In the first human trials conducted in the United States, palcitoclax showed safety, tolerance, and early anti-solid tumor effects Palcitoclax, as a new molecule, also exhibits predictable drug metabolic characteristics Given that the safety and effectiveness of Phase I trials are performing well, we look forward to further evaluating the anti-tumor effects of the drug in certain types of tumor diseases Dr Yang Dajun, Chairman and CEO of Asain Pharmaceuticals, said, "This presentation of a number of data at ASCO reflects the overall advancement of our global clinical development in the field of research and development of new drugs for apoptosis It is particularly exciting that combined drug data from MDM2-p53 inhibitors APG-115 and IAP inhibitor APG-1387 show considerable potential and are worth exploring further We will accelerate clinical development and look forward to providing more treatment options for clinical oncologists at an early date "