Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 896 |
| INN | Erfonrilimab |
| Status | Clinical |
| Drug code(s) | KN046 |
| Brand name | None |
| mAb sequence source | mAb chimeric/humanized |
| General Molecular Category | Bispecific |
| Format, general category | Fragment-Fc |
| Format details | 2+2 symmetric, (VHH-VHH')2-Fc, Tandem-VHH-Fc |
| Isotype (Fc) | IgG1 |
| Light chain isotype | None |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | Camelid-derived |
| Target(s) | PD-L1, CTLA-4 |
| Indications of clinical studies | Pancreatic Ductal Adenocarcinoma, Hepatocellular carcinoma, Gastro-intestinal tumors, thymic carcinoma, non-small cell lung cancer, triple-neg. breast cancer, solid tumors |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | May 21, 2018 |
| Start of Phase 2 | June 21, 2019 |
| Start of Phase 3 | September 14, 2020 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Alphamab (Australia) Co Pty Ltd. |
| Licensee/Partner | Pfizer, Zelgen, Sunny Lake, Kintor, Sinovent, InxMed |
| Comments about company or candidate | June 30, 2024: The NDA for KN046 is expected to be determined whether to be submitted in 2024, subject to the results of its final OS analysis for first-line treatment of sq NSCLC, and the one for KN026 is expected to be submitted in 2025. (https://www.alphamabonc.com/en/uploads/2024/08/172372714522178.pdf) Partners are Pfizer, Zelgen (泽璟)，Sunny Lake (东阳光)，Kintor (开拓)，Sinovent (信诺维)，InxMed (应世) April 4, 2023 Alphamab announces that KN046 enters the Pre-BLA phase: The Phase III clinical study of KN046 for the first-line treatment of advanced squamous non-small cell lung cancer achieved the preset endpoint of PFS, and the Phase III clinical study for the first-line treatment of advanced pancreatic cancer completed planned enrollment. We plan to submit two BLAs for KN046 in the treatment of sqNSCLC and PDAC in China in 2023. As of Sep 2022: Alphamab has initiated two pivotal clinical trials in NSCLC, a pivotal clinical trial in PDAC and a pivotal trial in thymic carcinoma. March 2022 presentation of YE2021 results: BLA planned in mid- 2022 (https://www.alphamabonc.com/en/uploads/2022/03/164856634734590.pdf) March 2021: Alphamab Oncology announced that U.S. Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug application (IND) to initiate an open label, multi-center phase II pivotal clinical study (NCT04469725; clinical trial No.: KN046-205) in the United States to evaluate the efficacy, safety and tolerability of KN046 (PD-L1/CTLA-4 bispecific antibody) for the treatment of thymic carcinoma. September 26, 2020 - Alphamab Oncology announced that Jiangsu Alphamab Biopharmaceuticals Co., Ltd., a wholly-owned subsidiary of the company, has achieved the first patient dosing in ENREACH-LUNG-01, a pivotal Phase Ⅲ clinical trial of KN046, a recombinant humanized PD-L1/CTLA-4 bispecific antibody invented and developed by Alphamab (Study code: ENREACH-LUNG-01). NCT04474119 Phase 3 in NSCLC started in Sep 2020. Sep 2020: Alphamab Oncology announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to KN046, a recombinant humanized PD-L1/CTLA-4 bispecific antibody developed by Jiangsu Alphamab Biopharmaceuticals, a wholly-owned subsidiary of the company, for the treatment of thymic epithelial tumors (TET). This is the second ODD awarded to Alphamab Oncology by FDA after the first ODD awarded to the subcutaneous PD-L1 antibody KN035 by FDA for the treatment of Biliary track cancer in early 2020. July 2020: Alphamab Oncology announced that Jiangsu Alphamab Biopharmaceuticals, a wholly-owned subsidiary of the Company, has entered a partnership agreement with Kintor Pharmaceutical to jointly develop the combination therapy of PD-L1 / CTLA-4 bispecific antibody KN046 and ALK-1 monoclonal antibody GT90001 in hepatocellular carcinoma (HCC). NCT04054531 Phase 2 study in NSCLC recruiting as of Sep 2019. NCT03925870 Phase 2 study in Esophageal Squamous Cell cancer recruiting as of June 21, 2019. NCT03838848 Phase 2 study in NSCLC not yet recruiting as of March 5, 2019. NCT03872791 Phase 1/2 study in triple-neg. breast cancer not yet recruiting as of March 13. NCT03529526 Phase 1 study started in May 2018. Oct. 10, 2018: Alphamab Oncology announced that its proprietary humanized PD-L1 - CTLA-4 bispecific antibody (product code: KN046) program, the first of its class, has recently started phase I clinical trial in Australia. The antibody has also obtained the IND approval from the National Medical Products Administration (NMPA) in China and will enter clinical trials in the country as well. |
| Full address of company | 218 Xinhu St. Building #C23, Suzhou, Jiangsu Asia China https://www.alphamabonc.com/en/contact/index.html |
Immune checkpoint targets. CRIB (Charge Repulsion Induced Bispecific). CRIB technology represents the 3rd generation of Fc-based bispecific platforms in engineering the Fc terminal of antibodies. To favor heterodimerization over homodimerization of the Fc, CRIB has introduced point mutations to induce changes in charge and H-bond interactions, in addition to steric interactions (Knob-in-Hole). The CRIB platform has been well validated by our HER2 bispecific program KN026*, which retains all the desirable features of a regular antibody, such as high yield at large-scale (3 g/L or above) standard production, full antibody function, and a stable product. https://www.alphamabonc.com/en/uploads/2023/08/169286574293454.pdf immunoglobulin G1 VH-VH-h-CH2-CH3 dimer, anti-[Homo sapiens CD274 (programmed death ligand 1, PDL1, PDL1, B7 homolog 1, B7H1)] and anti-[Homo sapiens CTLA4 (cytotoxic T-lymphocyte-associated protein 4, CD152)], chimeric and humanized monoclonal antibody, bispecific.
| Anticipated events | BLA in 2024 planned |
| Factor(s) contributing to discontinuation | None |