GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - APREA THERAPEUTICS INC

Financial Performance:

• The company maintains a cash runway extending to Q1 2028.
• Capital allocation from a financing round completed in March is dedicated to advancing the WE-1 inhibitor program through the first half of 2027.
• No specific revenue figures were discussed as the company is in clinical development phases; the focus remains on capital preservation for trial execution.

Guidance and Future Outlook:

• Near-term (2024-2025): Aiming to complete the Phase 1 dose escalation portion of the APRO 1051 study and initiate expansion cohorts within the next 1-2 quarters.
• Mid-term (2025-2026): Targeting enrollment of at least 50 patients in specific expansion cohorts (Uterine Serous Carcinoma and Cyclin E-overexpressing Platinum-Resistant Ovarian Cancer) to determine response rates.
• Long-term: Planning to engage the FDA regarding accelerated approval pathways based on Phase 2 data, contingent on demonstrated safety and efficacy in biomarker-selected populations.
• Pipeline Milestones: APRO 1051 is the primary focus; ATRN119 (ATR inhibitor) is transitioning to combination strategies with potential academic collaborations to be announced later this year.

Business Segments and Product Lines:

• APRO 1051 (WE-1 Inhibitor): A differentiated molecule designed for high selectivity against VE-1 while avoiding PLK1-3 inhibition to widen the therapeutic window and reduce toxicity (e.g., neutropenia).
• Clinical Status: Currently in Phase 1 dose escalation; demonstrated PK profile with a ~17-hour half-life and tolerability in heavily pre-treated patients.
• APRN119 (ATR Inhibitor): Completed dose escalation; shifting strategy from monotherapy to combination therapies (radiation/chemotherapy) due to suboptimal single-agent activity.
• Legacy Programs: Re-evaluating the p53 program for potential re-entry into the clinic based on patient demand and historical Phase 2 success.
• Preclinical: Novel DERC target currently in lead optimization.
• Combination Strategy: Adding arms for head and neck and colorectal cancers based on preclinical synergy with platinum-based therapies.

Market and Competitive Landscape:

• Target Validation: WE-1 is a clinically validated target; interest in the space benefits the field overall.
• Competitive Positioning: Aprea differentiates via selectivity and PK properties, contrasting with dual inhibitors that may have fixed ratios or broader kinome inhibition.
• Competitor Watch: Monitoring data releases from Zentalis and other WE-1 dual inhibitors, with expectations for Zentalis to report data in Q1 or H1 2025.
• Market Potential: Large total addressable market comparable to PARP inhibitors (e.g., Olaparib's >$3B annual sales), with potential for combination with chemo, IO, and ADCs.
• Biomarker Strategy: Focusing on specific genetic alterations (Cyclin E, FBXW7, PPP2R1A, USCs) to define the responder population and narrow the trial focus.

Risks and Challenges:

• Toxicity Management: Balancing therapeutic window against on-target neutropenia; efficacy at lower doses (150mg) without significant toxicity vs. higher doses (220mg).
• Trial Execution: Risk of slower enrollment or inability to identify the optimal dose/expansion population despite current site expansion (3 to 9 sites).
• Clinical Failure: Risk of insufficient efficacy in monotherapy (as seen with ATRN119) or inability to validate biomarker selection (IHC/PD biomarkers).
• Capital Efficiency: Cash runway covers operations only through Q1 2028; failure to meet milestones or secure partnerships could extend the timeline beyond this window.

Management Commentary and Tone:

• Tone: Cautiously optimistic and data-driven; management emphasizes that "biology and safety" will dictate the path forward rather than rushing development.
• Confidence: High confidence in the differentiation of APRO 1051 regarding selectivity and PK; willing to pivot strategies (e.g., ATR program to combinations) based on interim data.
• Strategy: Focus is on "Project Optimist" (FDA dose guidance), expanding sites to accelerate enrollment, and moving from wide dose escalation to focused expansion cohorts.

Analyst Questions and Answers:

• Q: How does APRO 1051 differ from class? A: Higher VE-1 selectivity avoiding PLK1-3 inhibition and optimized PK (17h half-life) to eliminate Cmax-related toxicity.
• Q: What are the dose thresholds for toxicity? A: First responses observed at 150mg (stable) and 220mg (confirmed PR); goal is to widen the window where efficacy exists without significant side effects.
• Q: What data to expect at Triple Meeting (Barcelona)? A: Expanded safety data from higher doses, PK profiles, and PD biomarker data from skin biopsies; increased site count from 3 to 9.
• Q: How will patient selection be refined? A: Utilizing IHC and genetic markers (Cyclin E, USC, FBXW7) to narrow the population; aiming for companion diagnostic partner agreements.
• Q: What is the strategy for the ATR program? A: Shift to combination with radiation/chemo due to monotherapy limitations; seeking academic collaborations.
• Q: Cash runway status? A: Extended to Q1 2028, covering the completion of dose escalation and initial expansion cohort enrollment.

Other Key Points:

• Site Expansion: Enrollment is tracking well with ~1 patient per site per month; currently ~8 patients in screening at any given time.
• Regulatory Path: Open to discussing accelerated approval with the FDA if Phase 2 data shows robust efficacy in biomarker-selected patients.
• Biomarker Validation: Plans to finalize companion diagnostic agreements for registration; initial IHC data for Cyclin E overexpression will be presented soon.
• Market View: Believes the WE-1 mechanism allows for diverse combination strategies (ADCs, IO) potentially surpassing current PARP inhibitor market dynamics if efficacy is proven.