SCIENCE
Pipeline
| Modality | Target | Indication | Development Status | |||
|---|---|---|---|---|---|---|
| Proof of Mechanism |
Hit to Lead |
Lead Optimization |
Pre-clinical | |||
| Multivalency Therapeutics |
PD-L1 x VEGF |
Solid Tumors (NSCLC, TNBC, etc) |
||||
| DR5 | Sarcoma | |||||
| Drug Encapsulation |
EGFR | Solid Tumors | ||||
| (new) | Solid Tumors | |||||
TSMT-PDVE is a multivalent PD-L1 × VEGF-targeting therapeutic designed to combine PD-L1 anchoring with spatial VEGF clustering, enabling dual and synergistic anti-tumor activity. The program has demonstrated comparable or superior MoA and anti-tumor efficacy compared to antibody-based cancer therapeutics, and lead optimization is currently underway.
Complementary
Biological Roles
- Immune checkpoint highly expressed on tumor cells
- Suppresses T-cell activation
- Provides tumor-selective anchoring for targeted therapy
- Drives tumor angiogenesis
- Promotes recruitment of immunosuppressive cells
- Normalizes TME
Synergistic Mechanism
in the TME
PD-L1 anchoring restores T-cell activation
VEGF clustering inhibits angiogenesis
Why T-sphaera for This
Combination?
- Multiple PD-L1 binders increase avidity on tumor cells
- Strong tumor retention
- Simultaneous presentation of multiple VEGF binders
- Efficient capture of VEGF within the TME
A single TSMT integrates both immune checkpoint and angiogenesis blockade to enhance anti-tumor efficacy.
ENCORE-EGFR is a multivalent EGFR-targeting drug encapsulation that combines multivalent target engagement with the encapsulation of cytotoxic payloads within the hollow cavity of T-sphaera. Proof-of-concept has been successfully demonstrated, providing a foundation for the development of our next ENCORE pipelines with diverse targets and payloads.
Confirmed stability of T-sphaera in 30% DMSO solution which demonstrated higher structural stability than antibody
Based on the comparison of molecular weights before and after conjugation of the linker and payload, it was confirmed that exactly 24 linker-payloads were conjugated per T-sphaera.
* Most ADCs are further limited by their slow internalization into the target cell (PDCs vs. ADCs: A New Frontier in Targeted Cancer Therapies and the Potential for Development Partnerships, ENDPOINTS NEWS)
Demonstrated higher cell penetration efficiency compared to ADCs