Excyte, a global clinical-stage biotechnology company, has achieved a significant milestone by dosing the first patient with YK012, the world's first T cell engager therapy to enter clinical trials for primary membranous nephropathy (pMN). The patient remained well after administration with no adverse reactions witnessed to date, according to the company's announcement on May 29, 2025.
Addressing a Critical Unmet Medical Need
Primary membranous nephropathy represents a substantial clinical challenge as an autoimmune disease caused by autoantibodies attacking podocyte antigens, leading to in situ immune complex formation. The condition stands as the most common cause of primary nephrotic syndrome in non-diabetic adults worldwide, accounting for 20% to 37% of affected individuals, with rates reaching as high as 40% in adults over 60 years of age.
Current treatment options face significant limitations, with 20-30% of pMN cases proving resistant to existing therapies such as rituximab and cyclophosphamide, while relapse rates remain problematically high. This treatment resistance underscores the urgent need for novel therapeutic approaches in this patient population.
Novel Mechanism of Action
YK012 represents a breakthrough as a bispecific CD19-directed CD3 T cell engager immunotherapy specifically designed for autoimmune diseases. The therapy functions as a T-cell engaging bispecific antibody targeting both CD19 and CD3, activating T-cell immunity via CD3 while targeting CD19—the most widely expressed tissue-specific marker during B-cell development, thereby enabling B-cell reset.
"Our data illustrated YK012 mediated significant B cell depletion and have illustrated in current clinical studies extended half-life and limited cytokine release in patients," said Andrew Meng, chairman and COO at Excyte. The therapy demonstrates milder T cell activation compared to Blincyto and exhibits target cell-dependent T cell activation, potentially offering improved safety profiles.
Clinical Development Progress
The study aims to evaluate the safety, tolerability, and preliminary efficacy of YK012 in pMN patients. Led by Professor Minghui Zhao and Professor Zhao Cui from Peking University First Hospital, the trial is planned across multiple centers in China. The clinical trial for this indication in the United States will be collaboratively executed by Excyte and its international partners.
YK012 obtained Clinical Trial Approval Notice (No. CXSL2400727) from China's National Medical Products Administration (NMPA) in December 2024 and was registered on ClinicalTrials.gov (NCT06982729). Excyte plans to file for US investigational new drug (IND) application imminently.
Broader Pipeline Implications
The successful initiation of YK012 in pMN extends Excyte's presence beyond oncology into autoimmune diseases. The company has demonstrated multiple complete response cases in ongoing relapsed/refractory non-Hodgkin lymphoma Phase Ia trials and relapsed/refractory acute lymphoblastic leukemia Phase Ib/II trials.
Earlier this year, Excyte secured clinical trial approval for systemic lupus erythematosus (SLE), with Professor Xiaofeng Zeng from Peking Union Medical College Hospital serving as Principal Investigator. A clear regulatory pathway in this orphan disease in the US could position YK012 as one of the first approved T cell engagers in the autoimmune space, with potential for expansion into additional autoimmune and oncology indications.
Company Background
Excyte was co-founded by Dr. Qing'an Yuan and Andrew Meng, biotech industry veterans with decades of antibody engineering experience. The company has established a U.S.-based wholly-owned subsidiary, Excyte LLC, forming a dual-engine drug R&D hub spanning China and the U.S. Excyte's FIST platform and next-generation assets feature long-acting, low-toxicity, and high-yield technological innovations for developing bispecific antibody drugs across hematologic cancers, multiple myeloma, solid tumors, and autoimmune diseases.
