Karyopharm Therapeutics (KPTI) Investor presentation summary

Endometrial cancer landscape and unmet need

• Molecular characterization guides treatment, but no approved therapies specifically target TP53 wild-type (TP53wt) endometrial cancer (EC) patients.

• TP53wt represents over 50% of EC cases, with pMMR accounting for 80% and dMMR for ~20%.

• Current maintenance therapies are not biomarker-driven, and checkpoint inhibitors show limited benefit in TP53wt/pMMR subgroups.

Selinexor mechanism and clinical development

• Selinexor is an oral XPO1 inhibitor that reactivates tumor suppressor proteins, notably p53, leading to selective cancer cell death.

• The SIENDO Phase 3 trial evaluated selinexor as maintenance therapy after chemotherapy in advanced or recurrent EC.

• SIENDO trial design included randomization to selinexor or placebo, with primary endpoint of progression-free survival (PFS).

Efficacy results from SIENDO trial

• In TP53wt subgroup, selinexor showed a median PFS (mPFS) of 28.4 months vs. 5.2 months for placebo (HR 0.44).

• In TP53wt/pMMR subgroup, mPFS was 39.5 months for selinexor vs. 4.9 months for placebo (HR 0.36).

• TP53wt/dMMR subgroup had mPFS of 13.1 months for selinexor vs. 3.7 months for placebo (HR 0.49).

• Promising overall survival signals observed, especially in TP53wt/pMMR subgroup (HR 0.48).