Precision Beyond Oncology: The Rise of MASP2 and TNFSF13 in Rare and Autoimmune Diseases

In July 2026, Nature Reviews published “Novel Drug Targets in 2025”, comprehensively sorting out innovative therapeutics approved in the year by four major drug regulatory authorities: the FDA, EMA, NMPA and PMDA. Data revealed that a total of 94 novel drugs (excluding vaccines and gene therapies) received marketing approvals throughout 2025. 11 novel drug targets with mechanisms of action (MoA) were identified, corresponding to 10 first-in-class drugs^[1]. A wide range of technical modalities were represented. Six small-molecule drugs feature multiple MoAs, including inhibitors, activators and nucleoside substrates. Three monoclonal antibodies target three major tracks: the complement pathway, autoimmune nephropathy, and infectious disorders. Notably, one peptide drug targeting mitochondrial phospholipids, pioneers an entirely new R&D pathway for lipid-targeted therapeutics.

The Landscape of Novel MoA Drug Targets in 2025

According to the report, the 11 first-in-class targets approved in 2025 span enzymes, kinases, tumor-associated antigens, neurotoxins, and phospholipids. Specific targets include DPP1, CTSL, MASP2, TNFSF13, CLPP, DCK/TK1, FAK1/PTK2B, Clostridium tetani neurotoxin, and cardiolipin. These distinct druggable sites address therapeutic indications across oncology, rare genetic disorders, autoimmune conditions, and infectious diseases.

Drugs with novel mechanism of action targets approved in 2025^[1]

Benchmark Commercial Targets: MASP2 and TNFSF13

Among these 11 pioneering targets, MASP2 and TNFSF13 have both undergone clinical and commercial validation via FDA-approved monoclonal antibodies. They respectively anchor the complement lectin pathway and the core autoimmune pathway in IgA nephropathy, representing core therapeutic areas combining groundbreaking innovation and substantial commercial prospects.

MASP2: The First Approved Target in the Complement Lectin Pathway

Narsoplimab, a MASP2-targeting agent, is the world’s first lectin pathway-specific monoclonal antibody, approved for transplant-associated thrombotic microangiopathy (TA-TMA). The drug directly binds MASP2 to block its activation via the MBL/MASP1 axis, abrogating the cascade of complement and inflammatory mediators upstream to prevent endothelial apoptosis triggered by IL-1/NF-κB pathway activation. Additionally, it restores the VEGF/ERK pathway to repair damaged vascular barriers. Notably, Narsoplimab exclusively acts on the lectin complement pathway without interfering with the classical and alternative complement pathways, which mediate the innate defense against infectious pathogens. This selective mechanism enables the drug to maintain an optimal balance between therapeutic efficacy and clinical safety.

Mechanism of action of Narsoplimab^[2]

TNFSF13: The First Targeted Therapy for IgA Nephropathy

Sibeprenlimab is the world’s first approved monoclonal antibody targeting TNFSF13 (APRIL) indicated for IgA nephropathy. As a core pathogenic mediator, TNFSF13 binds to BCMA and TACI receptors on B cells to induce the production of pathogenic Gd-IgA1, subsequently leading to the formation of immune complexes that deposit in the glomeruli and damage renal tissue. As a selective TNFSF13 inhibitor, Sibeprenlimab specifically binds and neutralizes TNFSF13 activity, thereby inhibiting plasma cell proliferation and antibody class switching to directly reduce the generation of Gd-IgA1 and halt renal injury at its source.

Mechanism of action of Sibeprenlimab^[3]

KACTUS High-Activity Recombinant Proteins Empower MASP2/TNFSF13 Drug Development

Against the backdrop of dual top-journal and clinical validation for MASP2 and TNFSF13, KACTUS has proactively laid out critical tool proteins for these two therapeutic areas, delivering complete, high-quality upstream R&D support for targeted drug development.

• Extensive Species Coverage: The product portfolio spans human, cynomolgus monkey, rat, mouse and more, seamlessly supporting cross-species validation from in vitro screening to non-human primate studies.
  
• Diverse Product Formats: Native monomer/active trimer variants, biotin-labeled products, ultra-low endotoxin grades and other variants are available, directly applicable to antibody screening, ELISA/SPR affinity measurement, neutralization assays, cellular functional verification and other workflows.
  
• High Activity & Purity: All proteins undergo rigorous SDS-PAGE purity analysis, SEC-HPLC aggregate testing and biological activity validation to guarantee batch-to-batch consistency and stability.
  
• Ultra-low endotoxin grades: Endotoxin levels for selected products are as low as 0.01 EU/mg, eliminating interference in animal immunization and endotoxin-sensitive cellular assays.
  

MASP2 Product List

TNFSF13 Product List

References

[1]  Avram S, Halip L, Curpan R, et al. Novel drug targets in 2025. Nat Rev Drug Disco. 2026;25,(7):503. doi: https://doi.org/10.1038/d41573-026-00102-9
[2] Elhadad S, Redmond D, Huang J, Tan A, Laurence J. MASP2 inhibition by narsoplimab suppresses endotheliopathies characteristic of transplant-associated thrombotic microangiopathy: in vitro and ex vivo evidence. Clin Exp Immunol. 2023;213(2):252-264. doi:10.1093/cei/uxad055.
[3] Perkovic V, Barratt J, Lafayette R, et al. Evaluating Sibeprenlimab in IgA Nephropathy - Rationale and Baseline Data from the VISIONARY Trial. Kidney Int Rep. 2025;10(12):4207-4218. doi:10.1016/j.ekir.2025.09.031.