GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - APREA THERAPEUTICS INC

Explicit Guidance:

• Cash Runway: Cash runway extends to Q1 2028.
• Capital Allocation: Funding raised in March is allocated to the WEE1 (APR 1051) program.
• Dose Escalation: Expected to complete the dose escalation portion of the study by H1 2026 (next year).
• Target Enrollment: Aiming for a minimum of 50 patients in the upcoming expansion cohorts for uterine serous carcinoma (USC) and Cyclin E-overexpressing endometrial cancer (PROC).
• Total Patient Exposure: Planning to enroll up to 100+ patients in the current Phase 1 dose expansion phase before moving to dedicated expansion.

Business-Segment Outlook:

• APR 1051 (WEE1 Inhibitor):
  • Development Path: Shifting from a wide Phase 1 dose escalation to a "mid-phase 2 building" dose expansion focused on biomarker-selected populations.
  • Biomarker Strategy: Focus on Cyclin E-overexpressing tumors (USC, PROC), FBXW7, and PPP2R1A alterations. IHC testing for these biomarkers is expected to go live soon.
  • Target Engagement: Will present PD biomarker data (skin biopsy) at the upcoming Barcelona meeting.
  • Monotherapy vs. Combination: Preclinical data supports combination with platinum for platinum-resistant tumors; FBXW7 and PPP2R1A cohorts will likely remain on monotherapy.
  • Expansion Indications: Prioritizing USC and Cyclin E-overexpressing platinum-resistant ovarian cancer.
  • Collaboration (ATR): Actively pursuing BD efforts for the ATR program (APR N119), with a target to announce one collaboration by the end of this year.
  • New Pipeline: Lead optimization ongoing for the DERC program (novel target); re-evaluating the legacy P53 program for re-introduction to clinic based on patient demand and internal work.
• Regulatory Milestones: Goal is to achieve Accelerated Approval based on Phase 2 data, which will trigger FDA registration discussions.

Market and Competitive Outlook:

• Competitive Landscape: Observing competitors (Merck, AstraZeneca, Zentalis) with interest in the WEE1 space; specifically, Zentalis data is expected in Q1 2026 or the first half of next year.
• Market Size: Projects a large TAM similar to PARP inhibitors (e.g., Olaparib >$3B annually), leveraging the mechanism's compatibility with chemo, IO, and ADCs.
• Differentiation: Emphasizes a selective WEE1 inhibitor (minimal PLK family co-inhibition) to widen the therapeutic window compared to earlier generation dual inhibitors.
• Landscape Trends: Cautiously optimistic regarding ADC emergence in platinum-resistant ovarian cancer; believes a biomarker-selected WEE1 strategy positions well for future combination therapies.

Macro / Industry Outlook:

• No specific commentary on broader macroeconomic factors, interest rates, FX, or regulations in the provided transcript.

Strategic Initiatives:

• Trial Expansion: Increased trial sites from 3 to 9 to accelerate enrollment.
• Enrollment Rate: Calculating approx. 1 patient per site per month, with ~8 patients currently in screening.
• Companion Diagnostic: Finalizing agreement with a leading pharma partner to serve as a companion diagnostic through registration.
• Academic Partnerships: Pursuing collaborations with academic institutions for the ATR program combination arms.
• P53 Program: Internal re-evaluation to identify specific patient subsets that previously benefited to facilitate a return to the clinic.

Risks and Headwinds to Outlook:

• Clinical Success: The "make or break" factor is the identification of the specific patient population that shows efficacy without side effects.
• Safety Thresholds: Therapeutic window determination relies on managing on-target toxicity (neutropenia); observed in patients at 150mg and 220mg doses.
• P53 Program History: Previous Phase 3 failure requires new identification of responsive patients before re-entry.
• Competitor Data: Future strategy will be influenced by data from Zentalis and other WEE1 competitors in the first half of next year.
• ATR Program Performance: Dose escalation showed unsatisfying activity as a monotherapy; the strategy is now entirely dependent on successful combination outcomes.

Management Tone on the Future:

• Confidence: Management expresses "cautious optimism" regarding the WEE1 landscape and combination potential.
• Strategic Focus: High confidence in the "biomarker-first" approach and the specific chemical differentiation of APR 1051 regarding selectivity and PK properties.
• Progress: Enthusiastic about enrollment speed and site activation; views the next 12 months as critical for inflection points regarding safety and activity data.
• Flexibility: Willing to pivot development paths (e.g., shifting ATR to combinations) based on clinical data rather than adhering to a fixed plan.

Miscellaneous:

• Next Data Read: Presentation of updated safety, PK, and PD biomarker data at the upcoming Triple Meeting in Barcelona.
• Scanning Frequency: Patients are scanned every two months; long-term durability data will not be fully available until later, but enrollment numbers will increase for the upcoming update.
• Targeted Toxicity: Neutropenia is expected as an on-target effect but is being managed through the widened therapeutic window provided by the new molecule's selectivity.