Preclinical Efficacy & Translational Readiness

Antitumor Activity

1. Potent cytotoxicity across multiple solid tumor models
2. Activity retained in drug-resistant cancer cell lines
3. Significant tumor growth inhibition in:
   1. Xenograft models
   2. Transgenic mouse models
4. Normal tissues spared, supporting a favorable therapeutic index

Pharmacokinetics & Distribution

1. IV administration
2. Rat half-life: ~2 hours
3. Large volume of distribution (Vss ~65 L/kg)
4. No formation of toxic 17-AG metabolite
5. PK profile supports once-weekly dosing

Pharmacodynamics

Clear PD evidence consistent with mitochondrial stress:

1. AMPK activation
2. Inhibition of mTOR/S6K signaling
3. Induction of a “cellular starvation” biomarker signature

This aligns well with modern biomarker-driven oncology development strategies.