Simcere Zaiming Licenses Global Rights of Novel CDH6-Targeting ADC SIM0505 to NextCure in Deal Worth Up to $745 Million

On June 16, 2025, it was announced that Simcere Zaiming, an oncology-focused innovative drug company under Simcere Pharmaceutical Group (HKEX: 2096), and NextCure, Inc. (Nasdaq: NXTC; hereinafter referred to as “NextCure”), a U.S. clinical-stage biopharmaceutical company dedicated to the development of innovative cancer therapies, have established a strategic partnership to jointly develop SIM0505, a novel antibody-drug conjugate (ADC) targeting CDH6 for the treatment of solid tumors.

Under the license agreement, NextCure will obtain global rights outside China for SIM0505, an innovative antibody-drug conjugate (ADC) targeting CDH6 developed by Simcere Biologics. This overseas licensing deal for SIM0505 serves as an initial validation of the value of Simcere Biologics’ ADC platform, marking the first international recognition of Simcere Pharmaceutical Group’s ADC technology platform.

As part of the collaboration, NextCure will also gain access to Simcere Biomedical’s proprietary topoisomerase I inhibitor payload technology for the development of another novel-target ADC product currently in preclinical development. Meanwhile, Simcere Biomedical will retain the rights to this novel-target ADC product in Greater China, further expanding its footprint in the oncology therapeutics landscape.

Under the terms of the agreement, Simcere is eligible to receive up to $745 million (over RMB 5.3 billion), including an upfront payment and development and sales milestone payments. In addition, Simcere will be entitled to tiered royalties on net sales of the product in markets outside China, with rates reaching up to double digits.

The current press release has not disclosed the financial terms. However, based on NextCure’s public SEC filings, certain details of the transaction terms are visible: a $12 million upfront payment, plus a conditional $5 million payment due by December 31, 2025, bringing the total near-term payments to $17 million.

It is reported that SIM0505 is currently undergoing Phase I clinical trials in China. NextCure plans to initiate clinical trials in the United States in the third quarter of 2025.

SIM0505 is a novel antibody-drug conjugate (ADC) targeting CDH6 (cadherin-6 or K-cadherin), developed by Simcere Neoxis. Its unique binding epitope confers higher affinity for the tumor antigen compared to peer candidate drugs. SIM0505 also incorporates Simcere Neoxis’s proprietary topoisomerase I inhibitor (TOPOi) payload, which delivers potent antitumor activity while exhibiting high systemic clearance, thereby widening the therapeutic window. Preclinical studies have demonstrated that the drug exerts strong tumor-inhibitory effects in various solid tumor models and shows a favorable safety profile in toxicology models.

CDH6 (Cadherin-6), also known as K-cadherin, is specifically localized to the basal outer membrane of epithelial cells and mediates calcium-dependent cell–cell adhesion. Its expression is minimal in normal adult tissues but is upregulated in various malignant tumors, including ovarian cancer and renal cell carcinoma. Overexpression of CDH6 has been associated with poor prognosis in multiple cancers, such as breast cancer, lung cancer, and renal cell carcinoma. Therefore, CDH6 represents a highly promising therapeutic target for novel anti-tumor drug development.

As a single-pass transmembrane protein, CDH6 features a large extracellular domain that facilitates antibody binding. Upon antibody engagement, it undergoes rapid internalization, acting as an “automatic delivery” system. An anti-CDH6 antibody-drug conjugate (ADC) can be conceptualized as linking an anti-CDH6 “navigating antibody” to a cytotoxic “bomb,” thereby precisely targeting cancer cells.

SIM0505 received the clinical trial approval notice issued by the China National Medical Products Administration (NMPA) on January 2, 2025, and is planned to conduct clinical trials for advanced solid tumors. The Investigational New Drug (IND) application for SIM0505 had already been approved by the U.S. Food and Drug Administration (FDA) on December 28, 2024.

It is worth noting that the current pipeline of antibody-drug conjugates (ADCs) targeting CDH6 is limited, and according to public information, no CDH6-targeted drugs have been marketed globally. Apart from Raludotatug deruxtecan (R-DXd/DS-6000), developed through the collaboration between Daiichi Sankyo and Merck, which has advanced to Phase II/III clinical trials, most other candidates remain in Phase I. Consequently, the field has not yet become a “red ocean” as fiercely competitive as those targeting TROP2 or CLDN18.2.

According toNextCureIn his remarks, President and Chief Executive Officer Michael Richman stated that this collaboration provides NextCure with the opportunity to advance the development of a novel CDH6-targeted antibody-drug conjugate (ADC). He further noted that Simcere’s proprietary payload is a potent cytotoxin that may offer superior safety and efficacy compared to other topoisomerase inhibitors.

NextCure is an innovative biotech company headquartered in Beltsville, Maryland, USA. Founded in 2015 by immunologist Dr. Lieping Chen, who currently serves as Chairman of its Scientific Advisory Board, the company’s core strategy is to develop “immune normalization therapy” products for cancers that are unresponsive or resistant to existing treatments, such as PD-1 inhibitors. Its key pipeline candidates include a LAIR-2 fusion protein (Phase I clinical trial) and a B7-H4 ADC (Phase I clinical trial).

It is widely acknowledged that the remarkable success of PD-1/PD-L1 therapy owes much to the contributions of Dr. Lieping Chen, who can even be regarded as the pioneer who translated PD-1/PD-L1 therapy from basic research into clinical application. In 1999, Dr. Chen published a paper in Nature Medicine reporting B7-H1 (later known as PD-L1), the third member of the B7 family and a protein that exerts negative regulation on immune responses. In 2002, he published another article in Nature Medicine, providing the first evidence that the B7-H1 pathway serves as a potential mechanism for tumor immune escape. These pivotal studies have earned Dr. Chen international recognition from the immunology and oncology communities for his outstanding contributions to the discovery of PD-L1 (B7-H1) and its application in cancer immunotherapy, thereby laying the foundation for the research and clinical use of PD-1/PD-L1 therapies.

NextCure was initially dedicated to the discovery and development of next-generation, first-in-class immunotherapies for cancer and other diseases. By leveraging its FIND-IO™ technology to functionally identify targets that may modulate immune responses, the company has established a novel immunotherapy development pipeline. On May 9, 2019, NextCure officially listed on the NASDAQ.

At the end of 2023, NextCure announced a strategic pivot to focus exclusively on antibody-drug conjugates (ADCs), licensing a B7H4-targeting ADC from LegoChem Biosciences. The current collaboration with Simcere has added a second ADC to its pipeline. NextCure believes that the licensed CDH6-targeting ADC possesses differentiated characteristics. Furthermore, beyond ovarian cancer, where this target is being explored for the first time, NextCure has highlighted opportunities for SIM0505 in other tumor types, including lung and renal cancers. Given the competitive landscape surrounding CDH6, emphasizing safety may serve as a direction to further enhance the differentiated advantages of SIM0505 in the future.

Notably, this collaboration marks Simcere’s second overseas licensing deal secured this year.

On January 13, 2025, Simcere NextMing and AbbVie entered into a licensing option agreement for the overseas rights to SIM0500, an independently developed trispecific antibody targeting GPRC5D, BCMA, and CD3. Leveraging a unique T-cell engager technology to activate the immune system, this therapeutic candidate is being evaluated in Phase I clinical trials concurrently in China and the United States for the treatment of relapsed or refractory multiple myeloma, and it was granted Fast Track designation by the U.S. FDA in 2024. The potential total transaction value of this collaboration amounts to $1.055 billion.

As early as September 29, 2022, Simcere announced that it had reached an overseas rights collaboration agreement with Almirall, Spain’s largest pharmaceutical company, for SIM0278, an IL-2 mutant fusion protein for the treatment of autoimmune diseases. The deal included an upfront payment of $15 million and milestone payments totaling $492 million, amounting to more than $500 million in all, setting a record at the time for the highest value of an overseas licensing deal for a preclinical autoimmune project from China. It is reported that Phase I clinical trials for this project are currently being conducted separately by Simcere and Almirall in China and the United States, targeting indications such as atopic dermatitis and other autoimmune diseases.

In line with Simcere’s innovative global expansion strategy, the company is centered on independent R&D and guided by global collaborations to gradually transform from a domestic pharmaceutical enterprise into an international innovator. Simcere’s core strategy involves promoting Chinese original drugs to the global stage through overseas licensing (License-out) of high-value pipelines and a global R&D layout, while leveraging international partners to accelerate the realization of innovative value.