Oncology Pipeline Addresses Unmet Needs
TUMOR-ASSOCIATED MACROPHAGES:
Solid Tumors Evade Immune System Due to Suppressive Cells; Drugs Fail to Target These Cells
THE NEED
- Even current “precision” medicine lacks the ability to only treat cancer cells, often killing healthy cells which leads to potentially toxic side effects, making the treatment less effective
- Most cancer drugs are unable to cross the blood brain barrier (BBB) to treat brain cancer
- Current immune therapies do not target tumor associated macrophages (TAMs), specific cells involved with the progression, spread, and inflammatory response of cancer
OUR SOLUTION
HDTs target inflammatory cells associated with cancer, delivering drugs only to tumors throughout the body, including the brain
Reduce side effects and allow for higher doses of drugs to reach cancer cells, making treatments more effective
Durable effects HDTs are retained inside TAMs – for up to 30 days, while healthy cells do not take in the drug
Approaches:
1 | 2 | 3 |
| Activate TAMs (heat tumors) | Inhibit Metastases | Irradiate Tumors (TAM reservoir) |
Tuning Our HDT to Optimize TAM Targeting
Construct Optimization: Single IV Dose in MC38 (Colon) Mouse Model
Targeting to Tumors:
- HDs optimized to achieve efficient uptake by M2 TAMs
- >60% of all M2 TAMs contain HD6 after single IV dose
- M1, mMDSCs and gMDSCs provide secondary targets (all other cells < 5%)
HDTs in Synthesis or Completed (SAR Design) – 21 Compounds
Cleland 2020; Liaw 2020
Preclinical Validation of Selective Brain Tumor Targeting and Persistence
Construct Optimization: Single IV Dose in MC38 (Colon) Mouse Model
Human Validation Strategy
D6-B483 Phase 1: Patients with GBM and Brain Metastases
- POC of tumor targeting across Blood Brain Barrier; leverage to select patients for HDTs
- Initiate Phase 1 in 2023
*Orthrotopic GBM (GL-261-luc)
High levels of reactive microglia/macrophage analogous to human GBM (Szulzewsky 2015)