Industrial Securities Co.,Ltd. released a research report stating that while TCE (T-cell engager) therapies have demonstrated efficacy and commercial viability in hematologic malignancies, several challenges remain. Innovations such as non-full-length bispecific antibodies, "2+1" format designs, TCR-based therapies, prodrugs, co-stimulatory targets, and selective T-cell targeting are enhancing TCE applicability in solid tumors. Domestic companies are actively advancing TCE development for solid tumors through platforms like CD28 co-stimulatory multispecific antibodies, TCE-ADCs, steric hindrance masking designs, and TCR therapies, forming a robust pipeline with diverse target strategies.
Key insights from Industrial Securities include: 1. **TCE in Hematologic vs. Solid Tumors**: Globally, 12 TCE therapies are approved (10 in the U.S., 6 in China), with 9 targeting blood cancers and only 3 for solid tumors. Challenges for solid tumors include: - Off-tumor toxicity risks to healthy tissues expressing tumor-associated antigens (TAAs). - Limited T-cell infiltration in the tumor microenvironment (TME). - Immunosuppressive TME factors like regulatory T cells and cytokine-induced T-cell exhaustion.
2. **Innovative Designs Enhancing Solid Tumor Applicability**: - **Non-Full-Length Bispecifics**: Amgen’s DLL3/CD3 bispecific (tarlatamab) and MSD’s gocatamig show promise in SCLC, including brain metastases. - **"2+1" Format**: Xencor’s XmAb platform enables precise CD3 affinity modulation, with Xaluritamig in Phase III and ENPP3 TCE validated in renal cell carcinoma. - **TCR-Based TCEs**: Immunocore’s FDA-approved KIMMTRAK (targeting gp100) highlights TCRs’ ability to target intracellular proteins with low antigen density. - **Prodrugs**: Janux’s masked peptide TCE (PSMA/mCRPC) and Vir’s VIR-5818 (HER2+) show early promise, with pH-dependent activation strategies (e.g., BioAlta’s EpCAM/CD3) improving safety. - **Co-Stimulatory Targets**: CD28 (Regeneron, Janux), 4-1BB, and CD2 (TCB EVOLVE-104) aim to amplify T-cell responses but require safety optimization. - **Selective T-Cell Activation**: AstraZeneca and Lava Therapeutics target CD8+ and Vγ9Vδ2 T cells to mitigate systemic immune toxicity.
3. **Domestic Progress**: Chinese firms are diversifying TCE platforms, with pipelines covering CD28 co-stimulation, TCE-ADCs, and TCR therapies. Companies to watch include Zegen Pharmaceuticals, LintonPharm, Hengrui Pharmaceuticals, Baili Pharmaceutical, Harbour BioMed, Fosun Pharma, and Antengene.
**Risks**: Unpredictable policy changes, intensifying competition, and R&D setbacks. Note: Industrial Securities serves as a market maker for Baili Pharmaceutical.
Comments