GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - APREA THERAPEUTICS INC

Explicit Guidance:

• Cash Runway: Extended through Q1 2028.
• Capital Allocation: Funds allocated through H1 2026 are designated to complete dose escalation and initiate expansion cohorts for the APRE-1051 program.
• Trial Completion: Expect to complete the dose escalation portion of the APRE-1051 study by H1 2026.

Business-Segment Outlook:

• APRE-1051 (WEE1 Inhibitor):
  • Dose Selection: Anticipated identification of two optimal doses for expansion within the next quarter or two following current dose escalation data.
  • Expansion Cohorts: Enrolling minimum 50 patients each for Uterine Serous Carcinoma (USC) and Cyclin E-expressing Platinum-Resistant Ovarian Cancer (PROC), utilizing immunohistochemistry (IHC) for patient selection.
  • Combination Arm Strategy: Initiating combination arms with standard-of-care therapies for Head and Neck Cancer and Colorectal Cancer (with MD Anderson collaboration), specifically targeting patients resistant to current regimens; monotherapy will be maintained for P53, FBXW7, and specific biomarker-positive cohorts.
  • Companion Diagnostic: Finalizing an agreement with a leading pharma partner to conduct the companion diagnostic through registration.
  • Milestone: Preparing to submit an inquiry to the FDA for an accelerated approval pathway based on Phase 2 data.
• ATRN119 (ATR Inhibitor):
  • Development Shift: Moving from monotherapy to combination therapies (radiation, chemotherapy) following unsatisfying monotherapy activity; seeking academic collaborations to announce within 2025.
• Other Assets:
  • P53 Program: Conducting internal analysis to identify patient responders from legacy Phase 2/3 data with the goal of returning the asset to the clinic.
  • DERC Program: Currently in lead optimization as a novel preclinical target.

Market and Competitive Outlook:

• WEE1 Landscape: Market opportunity compared to PARP inhibitors (e.g., Olaparib >$3B), leveraging potential for monotherapy and combinations with chemo, IO, and ADCs.
• Competitive Differentiation: Positioning APRE-119/1051 via high selectivity for WEE1 (avoiding PLK1/2/3 inhibition) to widen the therapeutic window compared to dual inhibitors.
• Competitor Timing: Anticipating data release from Zentalis (a key WEE1 competitor) in Q1 2026 or H1 2026.
• Treatment Paradigm: Cautiously optimistic regarding biomarker-selected strategies in platinum-resistant ovarian cancer amidst the emergence of ADCs, favoring combination approaches.

Macro / Industry Outlook:

• Regulatory Pathway: Aiming for accelerated approval based on Phase 2 data; engaging with the FDA regarding registration strategies.
• Clinical Trial Standards: Adhering to FDA Project Optimist guidance for dose selection and expansion.

Strategic Initiatives:

• Site Expansion: Increased clinical sites from 3 to 9 to accelerate enrollment; current enrollment rate is approximately one patient per site per month.
• Biomarker Refinement: Transitioning from wide Phase 1 dose escalation to focused expansion by finalizing IHC biomarkers (PPP2R1A, FBXW7, Cyclin E) to identify responders.
• Collaboration: Actively pursuing business development (BD) and academic partnerships for the ATR program in 2025.
• Data Generation: Sharing PD biomarker data (skin biopsy for target engagement) and PK data from higher doses at the upcoming Triple Meeting in Barcelona.

Risks and Headwinds to Outlook:

• Toxicity Profile: Continued monitoring of neutropenia (on-target effect) and ensuring the therapeutic window remains wide despite dose escalation.
• Development Uncertainty: APRE-1051 remains subject to dose-escalation outcomes; expansion relies on identifying a specific responsive patient population.
• Data Limitations: Upcoming Barcelona presentation will not yet include long-term durability data or confirmed responses from the first two scans due to the 2-month scanning interval.
• Competitive Pressure: Future strategy will be influenced by the efficacy and safety data released by competitors (specifically Zentalis) in H1 2026.

Management Tone on the Future:

• Confidence: Cautiously optimistic; management emphasizes that "biology is the rationale" and data will drive the transition from monotherapy to focused expansion.
• Strategic Focus: Highly confident in the selectivity of the WEE1 molecule to differentiate from class liabilities.
• Timeline: Clear and committed to a H1 2026 milestone for completing dose escalation and defining expansion cohorts.

Miscellaneous:

• Current Enrollment: Approximately 8 patients currently in screening; total program enrollment expected to reach ~100 patients or higher during the current phase.
• Biomarker Specifics: Focus on patients with E-overexpressing PROC, PPP2R1A, FBXW7, and USC alterations.
• Therapeutic Window: Key differentiator for APRE-1051 is the ability to inhibit WEE1 more potently without co-inhibiting PLK1, thereby avoiding Cmax-related toxicity and dose-limiting side effects.