Aprea Therapeutics (APRE) investor relations material

Synthetic lethality and APR-1051 design

• Development strategy pairs drugs with tumor-specific genetic alterations so cancer cells are vulnerable while normal cells remain viable; biomarkers guide patient eligibility.

• APR-1051 was designed for WEE1 selectivity over PLK1/2/3 and prolonged pharmacokinetics, aiming to reduce off-target toxicity and Cmax-related toxicity seen with earlier WEE1 inhibitors.

• Neutropenia may remain an on-target toxicity; selective WEE1 inhibition may widen the therapeutic window by avoiding PLK co-inhibition and higher dosing.

• APR-1051 has shown activity and tolerability; the ASCO update reported a ~17-hour half-life and a prolonged PK profile.

APR-1051 clinical development

• Dose escalation remains ongoing under FDA Project Optimus; two doses will be selected for expansion, with dose selection expected to be clearer in the next quarter or two.

• Stabilization began at 70 mg/day; a 150 mg dose produced the first PR with little associated toxicity, and a confirmed PR was seen at 220 mg.

• Upcoming Triple Meeting update was expected to cover expanded safety, additional enrollment, PK at higher doses, and skin-biopsy PD evidence of target engagement; enrollment sites increased from 3 to 9.

• The update was expected to include more patients and first-scan data, but limited long-term durability data because scans occur every two months and sites were recently added.

• Enrollment was described as strong, with ~8 patients screening at a time and ~1 patient per site per month; dose escalation completion and transition to focused expansion are planned by H1 next year.

Biomarkers, indications, and combinations

• Planned monotherapy cohorts include cyclin E-overexpressing platinum-resistant ovarian cancer (PROC), uterine serous carcinoma (USC), PPP2R1A, FBXW7, and TP53-altered colorectal cancer; the phase I may enroll up to 100 or more patients.

• At least 50 patients are planned across USC and cyclin E-overexpressing PROC cohorts, described as a mid-sized phase II effort within the phase I study.

• Biomarker data will guide a shift from broad dose escalation to focused expansion; an agreement with a leading pharma for a companion diagnostic was being finalized, with accelerated approval identified as a possible path.

• APR-1051 plus cisplatin showed strong preclinical synergy in a model resistant to both; combination enrollment is planned for patients resistant to both treatments, while selected biomarker cohorts remain on monotherapy.

• WEE1 may also combine with chemotherapy, immunotherapy, or ADCs; management expressed cautious optimism about combinations in PROC.