Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 91 |
| INN | Envafolimab |
| Status | Approved |
| Drug code(s) | KN035, ASC22 |
| Brand name | ENWEIDA, 恩維達® |
| mAb sequence source | mAb humanized |
| General Molecular Category | Naked monospecific |
| Format, general category | Fragment-Fc |
| Format details | VHH-Fc |
| Isotype (Fc) | TBD |
| Light chain isotype | None |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | Camelid-derived |
| Target(s) | PD-L1 |
| Indications of clinical studies | HIV infection, Metastatic or recurrent non-microsatellite highly unstable (non-MSI-H)/non-DNA mismatch repair defect (non-dMMR) endometrial cancer, Undifferentiated Pleomorphic Sarcoma, Hepatitis B, Bile tract carcinoma, solid tumors |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved China |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | January 15, 2017 |
| Start of Phase 2 | |
| Start of Phase 3 | October 15, 2018 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | 2021 |
| Date of first US approval | |
| INN, US product name | Envafolimab |
| US or EU approved indications | None |
| Company | Alphamab Oncology, 3D Medicines (Sichuan) Co. |
| Licensee/Partner | Glenmark, Simcere, TRACON Pharma., Ascletis Pharma Inc. |
| Comments about company or candidate | July 2024: Tracon is terminating further development of envafolimab because the objective response rate by blinded independent central review in the fully enrolled ENVASARC pivotal trial (NCT04480502) in the 82 evaluable patients is 5% (four responders) and did not meet the primary endpoint of 11%. January 25, 2024: Glenmark Specialty S.A. (GSSA), a subsidiary of Glenmark Pharmaceuticals Ltd. (Glenmark), announced the signing of a license agreement with JIANGSU ALPHAMAB BIOPHARMACEUTICALS CO., LTD (Jiangsu Alphamab) and 3D MEDICINES (BEIJING) CO., LTD. (3DMed), (together as the Licensors), for KN035 (Envafolimab) for India, Asia Pacific, Middle East and Africa, Russia, CIS, and Latin America. Sep 2022: FDA has granted fast track designation for the development of envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy. Accrual in the pivotal ENVASARC trial remains robust and we expect to report an independent data monitoring committee interim safety review [and interim efficacy review in the fourth quarter. June 2021: TRACON Pharmaceuticals, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to envafolimab, a novel, single-domain antibody against PD-L1, for the treatment of patients with soft tissue sarcoma. BLA in US anticipated in 2023. Jan 2021: New Drug Application (NDA) for envafolimab was granted priority review by the Center for Drug Evaluation of the National Medical Products Administration (NMPA) in the indication of MSI-H/dMMR cancer. Nov 2020: Alphamab Oncology and 3D Medicines, have submitted a new drug application (NDA) for the approval of envafolimab (KN035) in the indication of MSI-H/dMMR cancer to the National Medical Products Administration August 16, 2020 I Ascletis Pharma Inc. announces today dosing of the first HBV patient in Phase IIa clinical trial of ASC22, which is a first-in-class, subcutaneously administered PD-L1 antibody. ASC22(Envafolimab) Phase IIa clinical trial is a single dose escalation study with three subcutaneously administered doses (0.3, 1.0 and 2.5 mg/kg) to explore the safety and efficacy of ASC22(Envafolimab) in chronic hepatitis B patients (ClinicalTrials.gov Identifier: NCT04465890). As T cell exhaustion in chronic HBV infections is an important factor in immune tolerance, blocking the PD-1/PD-L1 pathway could be an effective immunotherapy approach to improve specific T cell function and lead to an effective clinical cure for chronic hepatitis B. There are 257 million people worldwide, including 70 million people in China, infected by HBV. May 2020: TRACON Pharmaceuticals announced the completion of a Type B pre-IND meeting with the U.S. Food and Drug Administration (FDA). The FDA agreed with TRACON’s proposals regarding key elements of the pivotal ENVASARC trial for envafolimab in the soft tissue sarcoma subtypes of undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS). April 2020: TRACON announced that the U.S. Food and Drug Administration (FDA) has granted TRACON a Type B Teleconference to take place on May 8, 2020 to discuss the trial design for a potential pivotal study of envafolimab in sarcoma . March 30, 2020 – Simcere Pharmaceuticals announced today that it has established strategic partnership with Jiangsu Alphamab Biopharmaceuticals Co., Ltd. ("Jiangsu Alphamab"), a wholly-owned subsidiary of Alphamab Oncology (stock code: 9966HK) and 3D Medicines (Beijing) Co., Ltd. ("3DMed") to advance the development and commercialization of KN035 (also known as envafolimab), a checkpoint inhibitor for programmed cell death ligand-1 (PD-L1), for oncology indications in mainland China. Jan 2020: Ascletis Pharma announced it obtained approval from the China’s National Medical Products Administration to conduct clinical trials of ASC22 in chronic hepatitis B patients in China. Dec 2019: TRACON Pharmaceuticals announced that it has signed a collaborative partnership agreement with 3D Medicines (Beijing) Co. and Jiangsu Alphamab Biopharmaceuticals, a wholly-owned subsidiary of Alphamab Oncology, for the development of envafolimab, also known as KN035, a PD-L1 single-domain antibody administered by subcutaneous injection, for development in soft tissue sarcoma in North America. June 2019: Phase 1 study results reported at ASCO Conclusions: KN035 exhibits a favorable safety profile and promising preliminary anti-tumor activity in patients with advanced malignancies. Clinical trial information: NCT03101488 (https://abstracts.asco.org/239/AbstView_239_266759.html). Jan. 13, 2019: Ascletis Pharma Inc. (Ascletis, 1672.HK) and Suzhou Alphamab Co., Ltd. (Alphamab) jointly announce today that Ascletis' subsidiary and Alphamab have entered into a strategic collaboration and exclusive licensing agreement for anti-PD-L1 KN035 to treat hepatitis B and other viral diseases in Greater China (Ascletis code: ASC22). NCT03478488 Phase 3 study listed as not yet recruiting, but as of October 23, 2018: Alphamab Oncology and 3D Medicines Inc. (3D Med) announced today PD-L1 antibody KN035 has entered late stage clinical development, including phase III for bile tract carcinoma (cholangiocarcinoma) and phase II for MSI-H solid tumors have been initiated in China. It is also announced that the poster entitled "Phase I Study of KN035, A Novel Fusion anti-PD-L1 Antibody Administered Subcutaneously in Patients with Advanced Solid Tumors in the USA" (poster No. 1456) was presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO). NCT03478488 Phase 3 Gemcitabine and Oxaliplatin With or Without KN035 for Biliary Tract Cancer: a Randomised, Open-label, Parallel-group, Multicenter study listed as not yet recruiting as of Oct 29 2018. Developed by Suzhou Alphamab Co., Ltd. IND filed in November 2016; NCT02827968 study Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors recruiting as of January 2017. In the US phase I trial, a total of 18 subjects were enrolled as of July 5, 2018. In the 17 subjects who finished efficacy evaluation, 2 partial response (PR) and 5 stable disease (SD) were confirmed, according to the RECIST1.1 criterion. No dose-limiting toxicity (DLT) was observed in this trial. The exposure to KN035 increased proportionally with dose. Average half-life of KN035 was about 200 hours. (poster No. 1456 presented at the 2018 Annual Congress of the European Society for Medical Oncology) |
| Full address of company | 175 Fangzhou Road, SIP, Suzhou, China Asia China https://www.alphamabonc.com/en/contact/index.html |
Immune checkpoint inhibitor. Fusion protein of anti-PD-L1 single domain antibody and Fc. immunoglobulin VH-h-CH2-CH3 gamma1 chain dimer, anti-[Homo sapiens CD274 (programmed death ligand 1, PDL1, PD-L1, B7 homolog 1, B7H1)], monoclonal antibody; gamma1 heavy chain VH-h-CH2-CH3 (1-360) [VH (Vicugna pacos IGHV3-3*01 (80.6%) -(IGHD) -IGHJ5*01 (92.3%)/Homo sapiens IGHV3-64*04 (78.4%) -(IGHD) -IGHJ1*01 (92.3%)) [8.8.21] (1-128) -Homo sapiens IGHG1*01 G1m1 (hinge 1-15, C5>S (133) (129-143), CH2 (144-253) D27>A (178), P116>G (244), CH3 D12 (269) L14 (271) (254-358), CHS (359-360)) (129-360)]; dimer (139-139":142-142")-bisdisulfide
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |