GX-BP1(SOX2-bioPROTAC)

Disease Indication

1. 1Monotherapy: Lung Squamous cell Carcinoma (LUSC)
2. 2Combination Therapy: Multiple Solid Tumors (Elimination/Reversal of resistance to anti-cancer Standard of Care (SOC) agents)

Development Stage

1. 1Confirmation of SOX2 target protein ubiquitination and proteasomal degradation
2. 2Confirmation of robust in vivo efficacy in a lung cancer xenograft animal model
3. 2Preparing the IND package utilizing LNPs for lung-specific delivery of mRNA

Summary

1. 1Lung Squamous Cell Carcinoma (LUSC) represents a market with significant unmet medical need and high growth potential due to the lack of effective therapeutic agents.
2. 2The only novel therapeutic approach to date that targets the SOX2 protein, which was previously considered "undruggable" by any existing therapeutic agent.
3. 2Offers significant potential for overcoming drug resistance when combined with standard-of-care agents.

Structure

This is a next-generation Targeted Protein Degrader (TPD) constructed as a direct fusion protein comprising a nanobody that specifically binds to the SOX2 protein and an engineered E3 protein. It possesses innovative differentiators compared to first-generation TPDs, such as small-molecule-based PROTACs.

Mechanism

1. 1GX-BP1 induces cancer cell death by selectively degrading the key oncogenic transcription factor SOX2 protein, which promotes proliferation, survival, invasion/metastasis, cancer stemness, and drug resistance. Furthermore, it acts to eliminate acquired resistance to standard-of-care agents in cancer cells.
2. 2mRNA-encoded GX-BP1 is delivered to the lungs via LNPs that have been confirmed for lung-specific delivery.

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Characteristics

SOX2 bioPROTAC (i.v., standard LNP) demonstrated robust in vivo efficacy in A549 and BxPC3 xenograft models.
"First-in-world demonstration of in vivo efficacy for an SOX2 degrader."

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SOX2 bioPROTAC (i.v., lung-targeted LNP) showed signs of anti-tumor activity in an A549 orthotopic model.

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