Aprea Therapeutics (APRE) investor relations material

WEE1 biology and therapeutic rationale

• Cancer cells accumulate DNA damage and replication stress, then may become unusually dependent on DNA repair pathways; disrupting those dependencies could exploit a therapeutic window versus normal cells.

• WEE1 acts as a DNA-replication checkpoint; inhibiting it in mutation-bearing cancer cells may trigger catastrophic failure during replication.

• Prior WEE1 inhibitor programs showed tumor-shrinking activity, but the central challenge is widening the efficacy-to-toxicity window enough for practical use.

Unmet need and patient populations

• Treatment options remain limited after standard therapy; uterine cancer and platinum-resistant ovarian cancer were highlighted as areas of substantial unmet need.

• WEE1 inhibition may exploit DNA damage caused by antibody-drug conjugates, potentially helping address resistance when used as a subsequent therapy; this remains a development rationale.

• Cyclin E overexpression was cited as the WEE1 biomarker with the most supporting data; ESMO data discussed showed survival of ~16 months versus ~7 months across the described platinum-resistant ovarian cancer groups.

• Other candidate markers include uterine serous carcinoma and mutations in CCNE1, CCNE2, FBXW7 and PPP2R1A; research is needed to clarify response rates by marker.

Market opportunity and class outlook

• Equity research estimated close to 20,000 potential U.S. monotherapy patients across populations with reported WEE1 activity, implying a $3B-$5B addressable market at standard pricing.

• Better tolerability could support combination studies and expand the addressable population beyond monotherapy; potential combinations include chemotherapy, immunotherapy and targeted therapies.

• First-generation inhibitors were associated with GI adverse events and myelosuppression; early work on newer inhibitors suggested myelosuppression may be reduced, pending confirmation in further studies.

• The panel identified confirmed responses, tolerability and durable benefit as key evidence; phase I/II cross-study comparisons are limited by patient heterogeneity.

• Multiple sponsors were expected to start combination studies in the coming months, with panelists optimistic about progress over the next 12-24 months.