Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Technical Presentation (2023)

14 slides from Karyopharm Therapeutics's technical presentation, 2023

  1. Slide 1: Selinexor Plus Ruxolitinib in JAKi-Naïve Patients With Myelofibrosis: Long-Term Follow-up From XPORT-MF-034

    Selinexor Plus Ruxolitinib in JAK Inhibitor (JAKi)-Naïve Patients With Myelofibrosis: Long-Term Follow-up From XPORT-MF-034 Suggestive of Disease Modification Srinivas K Tantravahi,1 Ashwin Kishtagari,2 Keri Maher,3 Sanjay Mohan,2 Josef T Prchal,1 Xulong Wang,4 Kamal Chamoun,5 Christopher J Walker,4

  2. Slide 2: Selinexor use in myelofibrosis is investigational and not approved

    The use of selinexor in myelofibrosis is investigational and not approved by any regulatory authority; the safety and efficacy of selinexor in myelofibrosis has not been established.

  3. Slide 3: A Wide Range of Unmet Needs Persist in Myelofibrosis (MF)

    A Wide Range of Unmet Needs Persist in Myelofibrosis (MF) MF is a heterogenous, progressive, and fatal disease characterized by splenomegaly and dysregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) and non-JAK/STAT pathways1-3 Underlying biological hallmarks of MF1:

  4. Slide 4: Selinexor is an Investigational Targeted Oral Exportin 1 (XPO1) Inhibitor

    Selinexor is an Investigational Targeted Oral Exportin 1 (XPO1) Inhibitor XPO1 Inhibition is a fundamental mechanism of action that may target both JAK/STAT and non-JAK/STAT pathways in MF Selinexor inhibits XPO1-mediated JAK-STAT pathway p53-driven cell death1 nuclear cargo protein export that may

  5. Slide 5: XPORT-MF-034: A Phase 1/3 Study of Selinexor Plus Ruxolitinib for JAKi-Naïve Patients With MF

    XPORT-MF-034: A Phase 1/3 Study of Selinexor Plus Ruxolitinib for JAKi-Naïve Patients With MF (NCT04562389) Phase 1a Phase 1b Primary endpoints: Dose escalation Dose expansion • Maximum tolerated Phase 3 dose / recommended Pivotal trial (N=306) Selinexor PO Selinexor PO Selinexor PO Phase 3 dose Ran

  6. Slide 6: Patient Demographics and Baseline Characteristics of Selinexor 60 mg QW Cohort

    Patient Demographics and Baseline Characteristics of Selinexor 60 mg QW Cohort* Selinexor 60 mg QW Selinexor 60 mg QW + ruxolitinib + ruxolitinib (N = 14) (N = 14) Demographics DIPSS risk, n (%) Age (years) median (min, max) 64.5 (58, 77) Intermediate-1 3 (21.4) Sex (female), n (%) 5 (35.7) Intermed

  7. Slide 7: Treatment-Emergent Adverse Events (TEAEs) of Selinexor 60 mg QW Cohort

    Treatment-Emergent Adverse Events (TEAEs) of Selinexor 60 mg QW Cohort* Selinexor 60 mg QW Prophylactic Antiemetic use Reduced the Incidence and Severity of Nausea TEAEs + ruxolitinib (N = 14) Nausea was transient in nature with a median duration ~2 cycles Any grade (≥ 30% overall), n (%) Nausea 11

  8. Slide 8: Spleen Volume Reduction (SVR) and Total Symptom Score (TSS) With Selinexor Plus Ruxolitinib

    Spleen Volume Reduction (SVR) and Total Symptom Score (TSS) With Selinexor (60 mg QW) Plus Ruxolitinib* SVR35 TSS50 Selinexor 60 mg QW + ruxolitinib​ Selinexor 60 mg QW + ruxolitinib​ ​Population Timepoint ​Population Timepoint n (%) n (%) Efficacy Week 12 10/12† (83) Efficacy Week 12 8/10‡ (80) eva

  9. Slide 9: Durability of SVR and TSS Responses With Selinexor Plus Ruxolitinib

    Durability of SVR and TSS Responses With Selinexor (60 mg QW) Plus Ruxolitinib* Duration of SVR Response† Duration of TSS Response‡ in Patients Treated With Selinexor 60 mg QW Plus Ruxolitinib who in Patients Treated With Selinexor 60 mg QW Plus Ruxolitinib who Achieved SVR35 Response at Week 24 as

  10. Slide 10: SVR and TSS With Selinexor and Suboptimal Dose of Ruxolitinib (≤5 mg)

    SVR and TSS With Selinexor (60 mg QW) and Suboptimal Dose of Ruxolitinib (≤5 mg)*,† SVR TSS Reduction‡ 0 weeks 12 weeks 24 weeks 0 weeks 12 weeks 24 weeks 0 0 10 10 Change in spleen volume from baseline (%) 20 n=5 20 Change in TSS from baseline (%) n=4 30 30 SVR35 40 40 TSS50 50 50 60 60 70 70 80 80

  11. Slide 11: Cytokine Reduction and Correlation With SVR After Selinexor Plus Ruxolitinib

    Cytokine Reduction and Correlation With SVR After Selinexor (40 or 60 mg QW) Plus Ruxolitinib TNF-𝝰 IL-1RA Selinexor Early decreases in proinflammatory cytokines observed 60 mg 40 mg Change cytokine at Week 4 (%) Change cytokine at Week 4 (%) by Week 4 in evaluable patients and sustained to end of…

  12. Slide 12: Variant Allele Frequency (VAF) at Week 24 With Selinexor Plus Ruxolitinib

    Variant Allele Frequency (VAF) at Week 24 With Selinexor (40 or 60 mg QW) Plus Ruxolitinib Change in VAF from baseline at Week 24 (%) 10 60 mg 60 mg 0 60 mg 60 mg 40 mg 40 mg 60 mg 60 mg 40 mg 40 mg 60 mg 40 mg 60 mg -10 -20 SVR anytime -30 SD SVR25 SVR35 -40 Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 Dr

  13. Slide 13: Conclusions

    Conclusions • In the Phase 1 portion of XPORT-MF-034, selinexor plus ruxolitinib had a generally tolerable and manageable side-effect profile, most common adverse events were nausea, anemia, thrombocytopenia, and fatigue • Encouraging signals of durable SVR and symptom improvement were observed with

  14. Slide 14: Acknowledgments

    Acknowledgments Thank you to the patients, caregivers, study sites, and study investigators To learn more about the ongoing clinical studies of selinexor in MF: Phase 3 part of the XPORT-MF-034: Study design poster Phase 2 selinexor monotherapy for patients with MF and moderate thrombocytopenia: Stu

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