Karyopharm Therapeutics (KPTI) Jefferies 2024 Global Healthcare Conference summary

Strategic and financial overview

• Positioned as a commercial-stage, innovation-driven oncology company with three Phase III programs expected to read out by 2025.

• Selinexor approved in over 40 countries, with 2024 global revenue guidance of $140M–$160M.

• Debt extended to 2028–2029, providing a cash runway through end of 2025.

• Focused resource allocation to core programs in endometrial cancer (EC), myelofibrosis (MF), and multiple myeloma (MM).

• Commercial business in MM showing positive growth, with 4% quarter-over-quarter increase and strong engagement.

Clinical data and program updates

• SIENDO Phase III trial in EC showed no benefit in ITT, but strong PFS benefit in p53 wild-type subgroup (28.1 vs 5.2 months, HR 0.44).

• In p53 wild-type, pMMR subgroup, selinexor achieved median PFS of ~40 months vs ~4 months for placebo (HR 0.36), outperforming checkpoint inhibitors.

• Q-TWiST analysis showed a 10.5-month benefit for selinexor, more than double that of dostarlimab.

• Ongoing XPORT-EC-042 Phase III trial enrolls only p53 wild-type patients, uses Foundation Medicine NGS for screening, and a lower 60mg dose with dual antiemetics.

• Top-line results for XPORT-EC-042 expected in H1 2025, with primary endpoint of PFS and a target delta of at least 6 months.

Treatment landscape and physician feedback

• Emerging treatment paradigm for p53 wild-type, pMMR EC: carboplatin, then selinexor, reserving checkpoint inhibitors for later lines.

• Majority of XPORT-EC-042 patients are pMMR (>60%), with similar demographics to SIENDO.

• Physician education ongoing to match therapies to molecular subtypes; KOLs recognize selinexor’s role in p53 wild-type, pMMR EC.

• Safety profile improved with lower dose and dual antiemetics; AEs like nausea are front-loaded and resolve early.

• PK modeling supports 60mg dose as maintaining efficacy while reducing grade 3/4 AEs by ~10%.