On May 31, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the company presented four posters of the latest clinical data on three of its drug candidates, including the MDM2-p53 inhibitor APG-115, novel Bcl-2/Bcl-xL dual inhibitor palcitoclax or APG-1252, and IAP inhibitor APG-1387, at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO20) (Press release, Ascentage Pharma, MAY 31, 2020, View Source [SID1234558754]).

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As a globally focused biotech company, Ascentage Pharma showcased the research advances of its drug candidates at ASCO (Free ASCO Whitepaper) for the third consecutive year and attracted global attention.

"In this Phase Ib study, the novel IAP antagonist APG-1387 was combined safely with pembrolizumab with a manageable adverse event profile. This represents an important milestone in the continued development of APG-1387," said Drew W. Rasco, MD, Associate Director of Clinical Research at the START Center for Cancer Care in San Antonio. "Furthermore, we observed some encouraging signs of clinical activity, which warrants further evaluation in specific patient populations, including microsatellite-stable colorectal cancer [CRC] and non-small-cell lung cancer [NSCLC]."

"Palcitoclax [APG-1252] is a novel and potent inhibitor of the Bcl-2 family of proteins and induces apoptosis in tumor cells. In the first-in-human Phase I trial in the U.S., palcitoclax has demonstrated safety and tolerability as well as preliminary evidence of efficacy in patients with solid tumors," said Nehal Lakhani, MD, PhD, START Center for Cancer Care（START Midwest）. "It also demonstrates predictable pharmacokinetics ideal for a new molecular entity. Given the promising evidence of safety and efficacy in the Phase I trial, further evaluation of efficacy in select solid tumors is warranted."

"Advanced liposarcoma is a common histological type of malignant soft-tissue sarcoma with poor prognosis and high recurrence rate, and there is lack of effective treatment options currently. APG-115 is a highly potent MDM2-p53 inhibitor, and our data on liposarcoma presented in last year’s ASCO (Free ASCO Whitepaper) report were promising," said Prof. Xing Zhang, Chief Physician of Melanoma and Sarcoma Medical Oncology Unit of Sun Yat-sen University Cancer Center. "In the updated data, a safety expansion at the 100-mg dose level was performed, and the recommended phase II dose [RP2D] was determined as 100 mg. These results support our previous findings that wild-type TP53 is a predictive biomarker of response to APG-115, and liposarcoma may be one of its potential target tumor types. We also look forward to more clinical studies and molecular biological evidence of APG-115."

"Through the showcase at ASCO (Free ASCO Whitepaper), Ascentage Pharma is demonstrating its capabilities of global clinical development in apoptosis. The initial data with our drug candidates, including MDM2-p53 inhibitor APG-115, novel Bcl-2/Bcl-xL dual inhibitor palcitoclax or APG-1252, and IAP inhibitor APG-1387, support further study with great potential in combination therapies," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "We will accelerate our clinical development programs, hoping to offer more treatment options for cancer patients with unmet medical needs."

Phase Ib study of a novel, small-molecule MDM2 inhibitor
APG-115 combined with pembrolizumab in U.S. patients with metastatic solid tumors
Abstract：#3512

APG-115-US-002 is an open-label, multi-center, Phase Ib/II study in U.S. , which was designed to assess safety, toxicity, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of APG-115 in combination with pembrolizumab in patients with advanced solid tumors. The Phase Ib dose-escalation study has been completed, and the Phase II is ongoing. The poster only reports the Phase Ib results.
As of April 1, 2020, in the Phase Ib study, 19 patients were treated with
APG-115 in 4 alternate-day (QOD) dose cohorts (50 mg, 100 mg, 150 mg, and 200 mg) in combination with pembrolizumab. No dose-limiting toxicities (DLTs) were observed. The maximum tolerated dose (MTD) was not reached, and the recommended Phase II dose (RP2D) of APG-115 combined with pembrolizumab was determined as 150 mg QOD according to safety data.
APG-115 in combination with pembrolizumab was generally tolerated. The most common treatment related adverse events (TRAEs) (>10%) included: nausea, fatigue, platelet count decreased, appetite decreased, vomiting, neutrophil count decreased, diarrhea, hypothyroidism, etc.
Antitumor effects were observed among 18 efficacy evaluable patients, including one patient with a confirmed complete response (CR) lasting for 20 months (still ongoing). Two patients had confirmed partial response (PR) for 8 to 9 months: of these, one patient with NSCLC failed 3 months, nivolumab therapy and the other had immunotherapy-naïve appendix cancer; seven patients had stable disease (SD) for 1.5 to 7 months. The objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.5%. Details of the patient with CR follows:
White female, age 55 years, diagnosed with stage IIIc serous-cell ovarian carcinoma in 2014, which recurred (as stage IV) within 6 months after surgery and platinum-containing adjuvant chemotherapy and then progressed on doxorubicin, topotecan + bevacizumab, and XMT1536 (ADC targeting NaPi2b) multiple lines of antitumor therapy, but still progressed. However, the patient had a PR after receiving APG-115 and pembrolizumab for 4 cycles, CR after 8 cycles, then maintain CR, now in 25th cycle of treatment. This patient has a family history of malignancy, with blood genetic tests showing wild-type TP53, ATM germline mutation.
PK analyses showed that AUC and Cmax generally increased dose proportionally over the dose range of 50 to 200 mg. Combining APG-115 with pembrolizumab did not appear to affect the PK of APG-115. PD analyses showed an increase in serum MIC-1 (biomarker of TP53 activation) that was dose dependent within the APG-115 dose ranges (50-200 mg).
Conclusion: Safety and efficacy data from this Phase Ib study demonstrated that APG-115 in combination with pembrolizumab is promising. The Phase II study is ongoing in the cancer patients with specific biomarker profiling.

Phase Ib study of a novel bivalent IAP antagonist APG-1387 in combination of pembrolizumab for patients with advanced solid tumors
Abstract：#3508

APG-1387-US-001 is an open-label, two-part, Phase I (APG-1387 monotherapy) and Phase Ib (APG-1387 in combination with pembrolizumab) study in U.S. Previous Phase I study showed that the MTD of APG-1387 single agent was 45 mg IV once weekly, and DLTs included elevated lipase and facial nerve disorder. This poster reports only Phase Ib results, including the safety, tolerability and preliminary efficacy of APG-1387 + pembrolizumab in patients with advanced solid tumors.
Through April 1, 2020, 41 patients with various advanced solid tumors had been treated with APG-1387 in combination with pembrolizumab, including 10 patients in dose escalation: 20 mg (n=4), 30 mg (n=3), and 45 mg (n=3); and 31 patients in MTD dose expansion. No DLT was observed during dose escalation, and the MTD of APG-1387 was determined as 45 mg.
APG-1387 was generally well tolerated with manageable adverse events when used in combination with pembrolizumab. Most common TRAEs (≥10%) included fatigue, headache, nausea, and maculopapular rash. Facial nerve disorder was seen in 2 patients (4.9%), which was not higher than in the single-agent study.
Antitumor effects: among 37 efficacy evaluable patients, 4 patients had PR (2 NSCLC, 1 CRC, and 1 breast cancer) and 12 patients had SD; the overall ORR was 10.8%, and the DCR was 43.2%. The NSCLC cohort achieved 50% ORR and 100% DCR. The CRC cohort achieved 50% DCR with 1 PR and 3 durable SD.
Preliminary PK data of APG-1387 showed dose proportionality in exposure (Cmax and AUC) over the dose range of 20 to 45 mg.
APG-1387 treatment induced rapid and significant cIAP-1/XIAP suppression, suggesting a potential PD effect.
Conclusion：The efficacy and safety data demonstrated that APG-1387 in combination with pembrolizumab is a promising approach and deserves further study in patients with advanced NSCLC and CRC.

First-in-human study of palcitoclax (APG-1252), a novel dual Bcl-2/Bcl-xL inhibitor, demonstrated advantages in platelet safety while maintaining anticancer effect in U.S. patients with metastatic solid tumors
Abstract：#3509

The study of palcitoclax (APG-1252) is a Phase I trial to characterize the safety, tolerability, PK, PD and preliminary anti-tumor effects of palcitoclax, and to determine the MTD/RP2D as well. Palcitoclax is intravenously administered twice per week (BIW) or once per week (QW) to patients with small-cell lung cancer (SCLC) and other solid tumors in a 28-day cycle, the standard "3+3" design was applied to dose-escalation stage. More patients will be included in the MTD expansion cohort after MTD/RP2D is determined.
As of December 21, 2019, 42 patients (31 on BIW and 11 on QW) with metastatic solid tumors had received APG-1252 treatment ranging from 10 to 400 mg in a 28-day cycle.
Four DLTs (Grade 4 thrombocytopenia) were judged by investigators at 400 mg and 320 mg. APG-1252 was well tolerated up to 240mg. MTD/RP2D was determined as 240mg QW.
Most adverse events (AEs) were G1 or G2, and 26.2% patients had ≥ G3 TRAEs. The most common TRAEs were platelet count decreased (14.3%), aspartate aminotransferase increased (9.5%), and alanine aminotransferase increased (7.1%).
Of 36 efficacy-evaluable patients, 3 patients with PR had relapsed SCLC, poorly differentiated neuroendocrine tumor of the prostate, or high-grade serous ovarian cancer. The patient with SCLC had PR that lasted for >18 cycles (dose level: 40 mg BIW). A total of 7 patients achieved SD, including 2 patients with SD lasting ≥ 6 cycles and 3 lasting ≥4 cycles. Another 26 patients had progressive disease at their first tumor assessment. The overall DCR was 27.8%.
APG-1252 displayed linear PK, which were approximately dose proportional over the dose range of 10 to 400 mg.
Conclusion: A sustainable antitumor effect was observed in this first-in-human study, which supports further development of palcitoclax (APG-1252) in combination with other therapies for solid tumors and hematological malignancies.

Phase I study results of APG-115, a MDM2-p53 antagonist, in Chinese patients with advanced liposarcoma and other solid tumors
Abstract：#11542

As of January 9, 2020, 21 eligible patients with advanced solid tumors were treated with APG-115 at 3 dose levels: 100 mg, 150 mg, and 200 mg. Liposarcoma comprised two-thirds of all tumors. Most of the 21 patients had completed ≥ 2 cycles of APG-115 treatment, and 1 patient had completed 6 cycles.
Efficacy assessment was performed in 19 patients (4 patients were still on treatment), including 13 with liposarcoma. Among these patients, 1 had a PR, and 12 had SD. The ORR was 5.3%, and the DCR was 68.4%. In patients with LPS and wild-type TP53 (n=9), the ORR was higher, reaching 11.1%, with a DCR of 77.8%.
Common treatment-emergent adverse events (TEAEs) included anemia and decreases in leukocyte and platelet counts. However, most AEs were G1 or G2, and the incidence of TEAEs was much lower at the 100-mg dose level.
This study found that, using a 21 day-on/7 day-off dosing schedule, APG-115 was generally safe and well tolerated especially at the 100-mg dose level. The RP2D was determined as 100 mg QOD.
Conclusion:

Evidence of single-agent clinical efficacy of APG-115 was observed in patients with LPS, as well as in patients with expression of wild-type TP53. Updated results of this study continue to support our previous interpretation that wild-type TP53 is a predictive biomarker of response to APG-115 in patients with LPS and other cancers.
The over 10 months’ duration of response observed in a patient with PR after treatment discontinuation suggests host immunomodulatory effects of APG-115 and also provides impetus for further evaluation of APG-115 as monotherapy or in combination with immunotherapy.
About APG-115
APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2-p53 protein-protein interaction (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 U.S., including a Phase I study as single agent, a Phase Ib/II study in combination with pembrolizumab for treatment of metastatic melanoma or advanced solid tumors, and a Phase I/II study as 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 single agent and a Phase Ib study as single agent or in combination with chemotherapy for treatment of AML (acute myelogenous leukemia) or MDS (myelodysplastic syndromes) are ongoing in China.

About APG-1387
APG-1387 is a novel small molecule inhibitor of apoptosis protein (IAP) antagonist that was discovered and is being developed by Ascentage Pharma. Ascentage is developing APG-1387 globally and has completed dose-escalation Phase I trials in solid tumors in China and Australia, and a Phase Ib/II clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the U.S. In addition, APG-1387 is being investigated in a Phase Ib trial for treatment of patients with CHB in China. In February 2020, APG-1387 was approved for a Phase Ib/II clinical trial in combination with chemotherapy for treatment of advanced pancreatic cancer.

About Palcitoclax or APG-1252
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.

On May 31, 2020 Taiho Oncology, Inc. reported efficacy and safety results of an interim analysis of FOENIX-CCA2, a single-arm multicenter Phase 2 study evaluating futibatinib (TAS-120) in patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements, who have failed at least one line of therapy (Press release, Taiho, MAY 31, 2020, View Source [SID1234558753]). The data were presented online at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from 10:30 a.m.-12:00 p.m. ET on Sunday, May 31, 2020.

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"The interim analysis demonstrated that treatment with the covalently-binding FGFR inhibitor futibatinib may lead to meaningful clinical benefit in patients with refractory iCCA with FGFR2 gene fusions or other rearrangements," said medical oncologist Lipika Goyal, MD , MPhil of the Massachusetts General Hospital Cancer Center. "In a disease with limited treatments, this drug could be an effective and well-tolerated option for patients and the oncologists that care for them."

In the FOENIX-CCA2 trial, 103 patients with locally advanced or metastatic unresectable iCCA harboring FGFR2 gene rearrangements including fusions who had received one or more prior lines of systemic therapy received futibatinib 20 mg once daily until disease progression or unacceptable toxicity. The primary endpoint of the trial is independent central radiology reviewed objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DOR) and safety. The interim analysis reported data for 67 patients (65%) with a minimum of 6 months of follow up and found the ORR was 37.3% (1 CR=1.5%; 24 PR=35.8%). Median duration of response was 8.31 months. The most common treatment-related adverse events (all grades, grade 3) at the time of analysis were hyperphosphatemia (80.6%; 26.9%), diarrhea (37.3%; 0%), and dry mouth (32.8%; 0%). There were no grade 4 treatment related adverse events. Final results from the trial will be presented at a future medical meeting.

"FOENIX-CCA2 adds to the body of evidence supporting futibatinib as a potential treatment option for patients living with intrahepatic cholangiocarcinoma," said Martin J. Birkhofer, MD, Senior Vice President and Chief Medical Officer, Taiho Oncology, Inc. "We are pleased to see the interim results of the FOENIX-CCA2 trial, which point to the efficacy and tolerability of futibatinib in these patients, and we look forward to sharing the final results and progressing this investigational compound."

In May 2018, the U.S. Food and Drug Administration Office of Orphan Drug Development granted futibatinib orphan drug status for the treatment of cholangiocarcinoma.

About Cholangiocarcinoma
Cholangiocarcinoma (CCA), also known as bile duct cancer, is not common. About 8,000 people in the U.S. are diagnosed with CCA each year.1 This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) cancers. CCA can occur at younger ages, but it is seen mainly in older people. The average age of people in the U.S. diagnosed with cancer of the intrahepatic bile ducts is 70, and for cancer of the extrahepatic bile ducts it is 72.2 The five-year survival rates of localized iCCA is 24%.1

The main treatment for CCA is surgery. Radiation therapy and chemotherapy may be used if the cancer cannot be entirely removed with surgery and in cases where the edges of the tissues removed at the operation show cancer cells (also called a positive margin). Both stage III and stage IV cancers cannot be completely removed surgically. Currently, standard treatment options are limited to radiation, palliative therapy, liver transplantation, surgery, chemotherapy and interventional radiology.2

About Futibatinib (TAS-120)
Futibatinib (TAS-120) is an investigational, oral, potent, selective, and irreversible small-molecule inhibitor of FGFR1, 2, 3, and 4 being studied as a potential treatment for patients with advanced solid tumors with FGFR1-4 genetic aberrations, including cholangiocarcinoma, who were previously treated with chemotherapy or other therapies. Futibatinib selectively and irreversibly binds to the ATP binding pocket of FGFR1-4 resulting in the inhibition of FGFR-mediated signal transduction pathways, reduced tumor cell proliferation and increased tumor cell death in tumors with FGFR1-4 genetic aberrations.

On May 31, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported the two-year follow-up results of TYVYT (sintilimab injection) ORIENT-4 study in relapsed or refractory Extranodal NK/T-cell lymphoma (nasal type) at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Abstract # 8050, Poster # 383, 8:00 AM – 11:00 AM, U.S. Central Time, Friday, May 29, 2020) (Press release, Innovent Biologics, MAY 31, 2020, View Source [SID1234558752]).

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ORIENT-4 is a multicenter, single-arm, Phase 2 clinical study evaluating the efficacy and safety of sintilimab in relapsed or refractory extranodal NK/T-cell lymphoma (nasal type). A total of 28 subjects were enrolled in the study, all of whom received sintilimab injection (200 mg, IV, Q3W). The study’s primary endpoint was objective response rate (ORR) based on Lugano 2014 response evaluation criteria.

As of January 17, 2020, the ORR was 67.9% and the complete response (CR) rate was 14.3%. The disease control rate (DCR) was 85.7% and the median overall survival (OS) had not been reached, which was 78.6% at two years, with no new safety signals identified.

Professor Jianyong Li, Director of Hematology Department at Jiangsu Provincial People’s Hospital, said "For patients with extranodal NK/T-cell lymphoma (nasal type) that do not respond to a L-asparaginase-containing regimen, there is no internationally recommended treatment regimen, resulting in an urgent clinical need to find effective therapeutic drugs to treat this disease. The results of the ORIENT-4 study showed that the ORR based on Lugano 2014 efficacy evaluation criteria was as high as 67.9% and the two-year OS rate was 78.6%. Sintilimab was statistically demonstrated the significant clinical efficacy in the treatment of relapsed or refractory extranodal NK/T-cell lymphoma (nasal type), and could bring long-term benefits to patients."

About TYVYT（sintilimab injection）

TYVYT (sintilimab injection), an innovative drug developed with global quality standards jointly developed by Innovent and Lilly in China, has been granted marketing approval by the National Medical Products Administration (NMPA) for relapsed or refractory classic Hodgkin’s lymphoma after second-line or later systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019.

TYVYT (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registration or pivotal clinical trials.

On May 31, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported the Phase 1b preliminary clinical study (NCT04072679) data of TYVYT (sintilimab injection) in combination with IBI305, a bevacizumab biosimilar independently developed by Innovent, in the treatment of advanced hepatocellular carcinoma at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)(Abstract # 3079, Poster # 143, 8:00 AM – 11:00 AM, U.S. Central Time, Friday, May 29, 2020) (Press release, Innovent Biologics, MAY 31, 2020, View Source [SID1234558751]).

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The NCT04072679 study, presented at the ASCO (Free ASCO Whitepaper) annual meeting by poster, was conducted by Professor Aiping Zhou from the Cancer Hospital Chinese Academy of Medical Sciences, and is a Phase 1b study assessing the safety, tolerability and anti-tumor activity of TYVYT in combination with IBI305 in subjects with advanced hepatocellular carcinoma, the most common form of liver cancer. The study was divided into two parts, the first is a dose escalation phase and the second is a dose expansion phase. In the dose escalation phase, according to the enrollment sequence, subjects will receive either 7.5 mg/kg (low-dose group) or 15 mg/kg (high-dose group) of IBI305 in combination with a fixed dose of 200 mg of sintilimab, respectively, and then entered into the dose expansion phase after completing the dose escalation phase. The main clinical data include:

As of January 7, 2020, a total of 50 subjects were enrolled, including 29 subjects in the low-dose group and 21 subjects in the high-dose group. 29 subjects in the low-dose group had at least two efficacy evaluations, of which 7 subjects had confirmed a partial response (PR), with objective response rate (ORR) of 24.1%; 18 subjects in the high-dose group had at least one efficacy evaluation, 6 subjects had a PR (1 unconfirmed, 5 confirmed), with an ORR of 33.3%.
Treatment-related adverse events (TRAEs) were mostly Grade 1-2, with the most common TRAEs including hypertension (28%) and pyrexia (26%); a total of 6 (12%) subjects experienced Grade ≥ 3 TRAEs, with the most common Grade ≥ 3 TRAE being hypertension (2 subjects).
Professor Zhou Aiping from Cancer Hospital Chinese Academy of Medical Sciences said："Hepatocellular carcinoma is a common malignant tumor in China. Most patients with hepatocellular carcinoma have entered into the advanced stage at time of diagnosis and are beyond the point where surgery could effectively remove all of the cancer. There is a long-term lack of effective treatment for advanced hepatocellular carcinoma. In recent years, with the rise of immunotherapy, immunotherapy combined with anti-vascular targeted therapy has attracted more and more clinicians’ attention, and multiple studies have shown outstanding clinical effects. This Phase 1b study preliminarily showed positive efficacy and good safety in patients with advanced liver cancer. Currently, there is a Phase 3 clinical trial of sintilimab in combination with IBI305 for first-line treatment of patients with advanced liver cancer ongoing, and we are hopeful to see positive results from this study to help more patients with liver cancer."

Dr. Zhou Hui, Vice President of Medical Science and Strategic Oncology of Innovent, said: "The combination of immunotherapy and anti-angiogenic therapy has a synergistic effect in the mechanism of action and is currently a hot spot for the clinical development of anti-tumor drugs. We are very pleased to see that sintilimab in combination with the bevacizumab biosimilar IBI305 has achieved preliminary positive efficacy in patients with advanced hepatocellular carcinoma and been showing the clinical application prospect of the combination of these two drugs in the treatment of liver cancer. We also hope that through our efforts, we can bring a new effective treatment option to patients in China with this type of cancer."

About TYVYT (sintilimab injection)

TYVYT (sintilimab injection), an innovative drug developed with global quality standards jointly developed by Innovent and Lilly in China, has been granted marketing approval by the National Medical Products Administration (NMPA) for relapsed or refractory classic Hodgkin’s lymphoma after second-line or later systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019.

TYVYT (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registration or pivotal clinical trials.

About IBI305 (bevacizumab biosimilar)

IBI305 is a biosimilar of bevacizumab injection, which is a recombinant human anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection, independently developed by Innovent. VEGF is an important factor in the angiogenic process and is overexpressed pathologically in the endothelial cells of most human tumors. Anti-VEGF antibody can selectively bind VEGF with high affinity, block the conduction of PI3K-Akt/PKB and Ras-Raf-MEK-ERK signaling pathways by blocking the binding of VEGF to receptors on the surface of vascular endothelial cells, thereby inhibiting the growth, proliferation and migration of vascular endothelial cells as well as angiogenesis, reducing vascular permeability, blocking the blood supply of tumor tissues, inhibiting the proliferation and metastasis of tumor cells, and inducing tumor cell apoptosis, so as to achieve anti-tumor therapeutic effect. On January 29, 2019, the NMPA accepted the New Drug Application (NDA) for IBI305 and was included in the priority review.

On May 31, 2020 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines, reported with Eli Lilly and Company (Lilly) (NYSE: LLY) the results of TYVYT (sintilimab injection) ORIENT-2 study, a pivotal clinical study of second-line treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Abstract # 4511, Poster # 119, 8:00 AM – 11:00 AM, U.S. Central Time, Friday, May 29, 2020) (Press release, Innovent Biologics, MAY 31, 2020, View Source [SID1234558750]).

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The ORIENT-2 study was a randomized, open-label, multicenter, Phase 2 clinical study comparing the efficacy and safety of sintilimab with chemotherapy (paclitaxel or irinotecan) in patients with advanced or metastatic ESCC whose disease progressed on first-line therapy. A total of 190 subjects were enrolled in the study and randomly assigned in a 1:1 ratio to receive either sintilimab injection or chemotherapy (paclitaxel or irinotecan). The study’s primary endpoint was overall survival (OS).

As of August 2, 2019, compared with paclitaxel/irinotecan, sintilimab demonstrated a statistically significant improvement in OS in the intent-to-treat (ITT) population (HR = 0.70, P = 0.032). The median OS in the sintilimab-treated group and the chemotherapy-treated group were 7.2 months and 6.2 months and the 12-month OS rates were 37.4% and 21.4%, respectively, showing encouraging antitumor efficacy in the sintilimab-treated group. The safety profile of sintilimab in this study of ESCC patients was similar to that seen in studies of sintilimab in other tumors.

Professor Jianming Xu, Director of the Department of Gastrointestinal Oncology at the Fifth Medical Center of PLA General Hospital, said: "For patients with advanced or metastatic ESCC who have progressed on first-line treatment, there are few next treatment options and traditional chemotherapy drugs have shown a very limited effect. The ORIENT-2 study confirmed that sintilimab can prolong OS compared with chemotherapy (paclitaxel or irinotecan) in the second-line treatment of patients with ESCC. We are hopeful that sintilimab can be used as an effective treatment option for the second-line treatment of ESCC, bringing more clinical benefits to patients in need."

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug developed with global quality standards jointly developed by Innovent and Lilly in China, has been granted marketing approval by the National Medical Products Administration (NMPA) for relapsed or refractory classic Hodgkin’s lymphoma after second-line or later systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019.

TYVYT (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registration or pivotal clinical trials.