Alaunos Therapeutics, Inc.

Two Complementary DIO Studies

The two DIO mouse studies that underlie this readout were designed to ask different questions and, taken together, describe a single multi-axis preclinical profile.

The longer-duration 48-day study (DIO Study 1) evaluated ALN1003 administered orally, twice daily, at a single dose level. It is in this study that the fullest expression of the multi-axis profile was observed — the coordinated metabolic profile referenced above — with treatment-associated changes spanning body weight, insulin-resistance biology (lower fasting insulin and lower HOMA-IR after adjustment for body fat), adipose endocrine signaling (higher adiponectin and adiponectin-to-leptin ratio), and hepatic biology (lower liver weight, lower ALT/AST/ALP, and qualitative liver histology findings consistent with lower hepatic steatosis).

The shorter 18-day dose-ranging study (DIO Study 2) evaluated ALN1003 administered in drinking water at low, medium, and high dose levels (middle and high doses were 3× and 9× the low dose, respectively). DIO Study 2 demonstrated dose-associated changes in body weight, body composition (preferential fat loss with higher lean percentage of body weight), liver weight, glucose, and total cholesterol. Interpretation of DIO Study 2 should consider dose-related reductions in water consumption and apparent dose aversion, which may confound attribution of effects solely to drug exposure in this administration paradigm; the Company is pursuing formulation optimization and dedicated PK/tolerability work.