Actuate Therapeutics (ACTU) investor relations material

Drug development highlights

• Oral elraglusib is advancing to clinical trials, aiming to improve upon IV results in difficult-to-treat cancers, especially metastatic pancreatic cancer, with significant efficacy and survival benefits demonstrated in over 500 patients.

• The oral formulation is expected to enhance patient exposure and outcomes, with 95% bioavailability and daily dosing, overcoming limitations of IV administration and patient compliance.

• Intellectual property protection extends to at least 2043, with the oral version potentially exceeding this due to ongoing registration review.

• The development strategy focuses on expanding indications, establishing a standard-of-care backbone in multiple cancers, and targeting rare pediatric cancers with high unmet need.

Clinical and preclinical data

• In first-line metastatic pancreatic cancer, combination therapy showed a 40% increase in median overall survival, doubling one-year survival, and a fivefold increase in two-year survival.

• Synergy with RAS inhibitors was demonstrated in preclinical models, with all tested cell lines showing additive or synergistic effects.

• Achieving a threshold plasma concentration of 210 ng/mL correlated with significantly better outcomes (hazard ratio 0.48), and the oral formulation is designed to help more patients reach this level.

• Subgroup analyses and exposure-response relationships reinforce the benefit of higher, sustained drug exposure.

Regulatory and operational plans

• IND clearance has been obtained for a phase I/II accelerated trial, with patient recruitment and site setup underway for a second-half-of-year start.

• The phase I/II study will evaluate monotherapy in refractory melanoma, non-small cell lung cancer, colorectal, and pancreatic cancer, with PK and RP2D as endpoints.

• EMA and FDA require full phase III trials for approval; the pivot to oral formulation aligns with the trend toward oral RAS inhibitors and combination regimens.