Link Cell Therapies Doses First Patient With Logic-Gated CAR-T LNK001 in Clear Cell RCC
核心洞察
Link Cell Therapies (搜索) has begun clinical dosing of LNK001, an AND-gated CAR-T therapy targeting CAIX (搜索) and ENPP3 (搜索), in a Phase 1 study at MD Anderson Cancer Center.
The trial enrolls patients with advanced or metastatic clear cell renal cell carcinoma (搜索), the first clinical test of the company's logic-gating platform.
Link upsized its Series A financing from $60 million to $90 million to fund a second solid tumor program in colorectal cancer (搜索) with a first-in-human trial planned for 2027.
Link Cell Therapies (搜索) has initiated clinical dosing for its lead program, LNK001, in a Phase 1 study at MD Anderson Cancer Center in patients with advanced or metastatic clear cell renal cell carcinoma (搜索). The South San Francisco-based oncology cell therapy company said the study is the first clinical test of its proprietary logic-gating technology, which is designed to improve the ability of CAR-T therapies to distinguish cancer cells from healthy tissue.
LNK001 is an AND-gated CAR-T therapy that requires co-expression of two antigens, CAIX (搜索) and ENPP3 (搜索), before triggering its CAR-T response. According to Link, both antigens are highly expressed together in most renal cell carcinoma tumors. Additional clinical trial details are available under the identifier NCT07564232.
Targeting a Long-Pursued Renal Cancer Antigen
CAIX (搜索) has long been among the most attractive targets in renal cell carcinoma, but conventional CAR-T cells directed against it have been limited by on-target, off-tumor toxicity in the biliary epithelium, where CAIX is also expressed. By gating CAR-T activity on both CAIX and ENPP3 (搜索), LNK001 is designed to preserve the antitumor potential of CAIX targeting while sparing the healthy tissue that has constrained single-antigen approaches.
LNK001 is manufactured at CTMC (搜索), a joint venture between Resilience (搜索) and The University of Texas MD Anderson Cancer Center.
Leadership Team Built Out for Clinical-Stage Operations
The company named Jie D'Elia, Ph.D., as chief executive officer and a member of its board of directors. D'Elia was previously CEO of SystImmune (搜索), a clinical-stage biopharmaceutical company developing multi-specific antibodies and antibody-drug conjugates. Before that she spent eleven years at Bristol Myers Squibb (搜索), most recently as senior vice president of business development for oncology, hematology and cell therapy. Her earlier roles include vice president and global head of business development at Simcere Pharmaceutical (搜索), and positions at AstraZeneca, Boston Consulting Group and Baxter Healthcare. Link said she has led more than $40 billion in strategic partnerships and acquisitions over her career.
"Link's logic-gate platform can make CAR-T broadly viable in solid tumors," D'Elia said. "A targeting approach that reliably distinguishes tumor from healthy tissue is what allows CAR-T to pursue in solid tumors the kind of deep and durable responses it has achieved in hematologic cancers. This financing lets us advance a pipeline built on that approach across additional tumor types."
Friedrich Graf Finckenstein, M.D., joined as chief medical officer. He most recently served as chief medical officer of Iovance Biotherapeutics, where he advanced a clinical portfolio of tumor-infiltrating lymphocyte therapies and contributed to the approval of AMTAGVI (lifileucel) in the United States, Canada and Australia as the first approved cell therapy for a solid tumor. Before Iovance, he was global head of oncology translational medicine at Roche Pharma Research and Early Development in Basel, Switzerland, and earlier held clinical leadership roles at Bristol Myers Squibb (搜索), including contributions to the approval of Opdivo (nivolumab) in lung cancer.
Co-founder Brian Slingerland, who started Link in 2022 with Robbie Majzner, M.D., and Crystal Mackall, M.D., becomes executive chair. He previously co-founded and served as CEO of Stemcentrx (搜索), an antibody-drug conjugate company that pursued targets with limited or no normal tissue expression, including DLL3 (搜索) and SEZ6 (搜索). AbbVie acquired Stemcentrx in 2016 for $6.2 billion.
"From the beginning, our vision has been to translate this breakthrough science into therapies that can make a profound difference for people impacted by cancer," Majzner, of the Dana-Farber Cancer Institute and Harvard Medical School, said. "Bringing in leaders with the experience, commitment and passion to advance our technology and execute at scale gives me tremendous confidence that we can realize that vision."
Abraham Bassan, a member of the Link board of directors and a partner at Samsara BioCapital (搜索), said the depth of the leadership team puts the company in a position to develop a new generation of medicines for patients.
Series A Reaches $90 Million
Link expanded its previously announced $60 million Series A financing to $90 million. The original round was led by Johnson & Johnson through its corporate venture capital organization, Johnson & Johnson Innovation - JJDC, with participation from founding investors Samsara BioCapital (搜索) and Sheatree Capital (搜索), as well as Wing Venture Capital (搜索). New investors include Bristol Myers Squibb (搜索), Kyowa Kirin, Sherpa Healthcare Partners (搜索), Western Technology Investment (搜索) and the MD Anderson Cancer Focus Fund (搜索).
The additional capital will support clinical and preclinical development of further logic-gated CAR-T programs. Link's second solid tumor indication is colorectal cancer (搜索), where it intends to begin a first-in-human trial in 2027 using a novel target pair that is co-expressed in the majority of colorectal tumors but absent from normal healthy tissues. Additional CAR-T programs in solid and hematologic cancers are in earlier development and will be advanced internally or through partnerships.
Link's logic-gating technology is intended to allow safe targeting of multiple antigens co-expressed selectively on cancer cells, reducing the risk of on-target, off-tumor toxicity. The company said the approach enables discovery of new "clean" target pairs for next-generation CAR-T therapeutics in solid and hematologic cancers.