Project ID:BP-20240708-OR-72
Product Brief Summary
- Product Name: ANTI-CDCP1 mAb and ADC
- Modality: Antibody and ADC
- Target: CDCP1
- Therapeutic Area: Oncology
- Current Stage: PCC
- Rights Available: China/Global Right
- Collaboration Mode: License out
CDCP1 is a promising anti-tumor target
- CUB domain containing protein 1 (CDCP1) is a type I single-pass membrane protein that is highly overexpressed in a variety of solid tumors (e.g., colon, pancreatic, breast, kidney).
- CDCP1 is upregulated and functionally critical in KRAS-mutant tumors, promoting tumor growth, metastasis, and resistance.
- Elevated CDCP1 expression has been correlated with poor outcomes in multiple tumor types.
CDCP1 is widely expressed in solid tumor but limited in normal tissue
- CDCP1 mRNA is Highly Expressed in Certain Tumor Tissues
- CDCP1 Protein is Highly Expressed in Corresponding Tumor Tissues
- CDCP1 High expression rate
Segregation of IHC Scores into “Low” (≤100), “Medium” (>100 to 200) and “High” (≥200 to 300)
- 97.2% Colon cancer
- 88.6% Pancreatic cancer
- 60.6% Lung cancer
- 58.7% Bladder cancer
- 57.1% Breast cancer
CDCP1 in CRC: high expression and chemo-resistance
- Robust expression of CDCP1 in primary CRC samples vs normal samples
- CDCP1+ cancer stem cells in muKras CRCs
- selectively enriched following chemotherapy;
- define a quiescent subpopulation exhibiting lower levels of intracellular ROS, which accounts for their resistance to chemotherapeutic drugs.
- CDCP1 ADC (ch10D7-MMAE) is effective against in vivo CRC models
Highlights of Anti-CDCP1 mAb: ADC Case
- Fully humanized mAb binds to cell surface CDCP1 with an affinity of ~ 0.1 nM regardless of CDCP1 cleavage status,which is more potent than the benchmark 14A043.
- Faster internalization rate (more than 70% at 4 hours) compared to benchmarks 10D7 and 14A043.
- In vitro potency in the picomolar to sub-nanomolar IC50 range for cytotoxicity to CDCP1 expressing cell lines, more potent than benchmark 14A043.
- In vivo striking efficacy comparable to benchmark 10D7.
- Long half-life of 283.6 hours (~12 days), meeting drug development requirement.
The mAb showed excellent binding ability to CDCP1 regardless of the cleavage status
The mAb showed excellent internalization rate: The mAb can induce rapid and endurable CDCP1 internalization.
The ADC showed specific cytotoxicity to cells with various CDCP1 expression
The ADC showed striking in vivo efficacy
The ADC showed desirable PK profile
- The candidate exhibited long half-life (T1/2 =283.6 hrs, ~12 days) and slow clearance rate (cl= 0.25 mL/hr/kg), making it favorable for drug development.
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