Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — Technical Presentation (October 2020)
17 slides from Karyopharm Therapeutics's technical presentation, Oct 1, 2020
Slide 1: Treatment of Severe COVID-19 with Low-Dose Selinexor
Treatment of Severe COVID-19 with Low-Dose Selinexor: Demonstration of Anti-Viral and Anti-Inflammatory Activities in a Randomized, International, Multicenter, Placebo-Controlled Phase 2 Clinical Trial George Geils Jr., Zainab Shahid, Don Stevens, Nathan C. Bahr, Jacek Skarbinski, Vaishali Sanchoraw
Slide 2: Disclosures – George Geils Jr.
Disclosures – George Geils Jr. Research Support None Consultant None Honoraria None Scientific Advisory Board None Major Stockholder None Amgen, Celgene, Janssen Oncology, and Sanofi Speakers Bureau Genzyme ©2020 Karyopharm Therapeutics Inc. 2
Slide 3: Exportin 1 (XPO1): Viral replication
Exportin 1 (XPO1): Viral replication • Exportin 1 (XPO1) mediates SARS-CoV-2 lifecycle and proinflammatory transcription factors • XPO1 has been identified as a “hub” host protein for SARS-CoV propagation. • XPO1 plays a central role in inflammation through regulation of the NF-kB and COX-2 pathways
Slide 4: Selinexor (XPOVIO) XPO1 Inhibition: Unique Dual Mechanism of Action
Selinexor (XPOVIO®️) XPO1 Inhibition: Unique Dual Mechanism of Action with Anti-Viral and Anti-inflammatory Activities ©2020 Karyopharm Therapeutics Inc. 4
Slide 5: Selinexor Inhibits SARS-CoV-2 Viral Propagation
Selinexor Inhibits SARS-CoV-2 Viral Selinexor Decreases SARS-CoV-2 Viral Propagation and Shedding and Induces Load and Severity of Rhinitis and Lung Nuclear Accumulation of ACE2 In Vitro Inflammation In Vivo Rhinitis Alveolitis ©2020 Karyopharm Therapeutics Inc. 5
Slide 6: XPORT-CoV-1001: A Phase 2 Randomized Single-Blind Study
XPORT-CoV-1001: A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients with Severe COVID-19 ~70 International Study Sites, ~8 countries 2 interim analyses (~74 randomized and ~124 randomized) Oral Selinexor 20 mg Days 1, 3, and 5
Slide 7: Inclusion Criteria
XPORT-CoV-1001: Inclusion Criteria Eligible patients had symptoms of severe COVID-19 as demonstrated by: At least 1 of the following: Clinical signs indicative of lower • Fever respiratory infection with COVID-19, • Cough with at least 1 of the following: • Sore throat • SpO2 ≤92% or requires ≥4 LPM
Slide 8: XPORT-CoV-1001: Patient Characteristics (ITT)
XPORT-CoV-1001: Patient Characteristics (ITT) CHARACTERISTIC N = 117 Age, years Median, (range) 55.0 (25-98) Sex, n (%) Male 68 (58.1) Concomitant Therapies, n (%) Remdesivir 59 (50.4) Hydroxychloroquine 1 (0.9) Systemic corticosteroid 54 (46.2) IL-6 inhibitor* 10 (8.6) No. of High-Risk Comorbiditie
Slide 9: XPORT-CoV-1001: Treatment-Related Adverse Events (ITT)
XPORT-CoV-1001: Treatment-Related Adverse Events (ITT) Selinexor Placebo n, (%) N=65 N=50 Grade 1/2 Grade 3 Grade 4 Total Grade 1/2 Grade 3 Grade 4 Total Any Treatment-Related 14 (21.5) 4 (6.2) 1 (1.5) 19 (29.2) 8 (16.0) 2 (4.0) 0 (0) 10 (20.0) Adverse Event Hematological Hyponatremia 3 (4.6) 1 (1.5
Slide 10: Efficacy (ITT)
XPORT-CoV-1001: Efficacy (ITT) Selinexor Placebo Parameter N=66 N=51 n (%) n (%) Probability of PCR Negative Conversion Clinical improvement Day 14 35 (53.0) 28 (54.9) (2-point improvement in ordinal scale), n (%) Time to clinical improvement (2 points), 11.0 9.0 median days (range) (9.0, 16.0) (8.0
Slide 11: XPORT-CoV-1001: Safety Outcomes (Low LDH/DD)
XPORT-CoV-1001: Safety Outcomes (Low LDH/DD) Low LDH/DD* High LDH/DD* Parameter Selinexor Placebo Selinexor Placebo N=38 N=27 N=27 N=23 n (%) n (%) n (%) n (%) Patients with at least 1 AE 24 (63.2) 14 (51.9) 21 (77.8) 12 (52.2) Patients with at least 1 3 (7.9) 1 (3.7) 6 (22.2) 7 (30.4) Grade 3/4 AE
Slide 12: Efficacy – Selinexor improved clinical status as compared with placebo
XPORT-CoV-1001: Efficacy – Selinexor improved clinical status as compared with placebo (Low LDH/DD) Low LDH/DD* High LDH/DD* Parameter Selinexor Placebo Selinexor Placebo N=38 N=28 N=28 N=23 n (%) n (%) n (%) n (%) Hospital Discharged by Day 14 30 (78.9) 16 (57.1) 13 (46.4) 14 (60.9) OSI-2 by Day 14
Slide 13: Efficacy – Selinexor improved PCR negative conversion rate
XPORT-CoV-1001: Efficacy – Selinexor improved PCR negative conversion rate and time to PCR negative as compared with placebo (Low LDH/DD) Low LDH/DD* High LDH/DD* Parameter Selinexor Placebo Selinexor Placebo N=38 N=28 N=28 N=23 n (%) n (%) n (%) n (%) Converted to PCR negative status 16 (42.1) 8 (2
Slide 14: Selinexor reduces cytokines associated with COVID-19
XPORT-CoV-1001: Selinexor reduces cytokines associated with COVID-19 (Low LDH/DD) IL-1RA IL-6 IL-7 IP-10 * * * * TNFa Selinexor Placebo Parameter N=38 N=28 n (%) n (%) LDH 11/34 (32) 3/24 (13) * D-dimer 21/34 (62) 13/25 (52) CRP 19/38 (50) 12/25 (48) ©2020 Karyopharm Therapeutics Inc. 14
Slide 15: Summary and Conclusions
XPORT-CoV-1001: Summary and Conclusions • XPO1 is an important target with and critical role in viral replication cycle • Selinexor has demonstrated anti-viral activity in vitro and in vivo • Selinexor protects healthy cells from infection via reduction in ACE receptor expression on cell surface • O
Slide 16: Acknowledgements
Acknowledgements Patients, their Families, and Caregivers Investigators, Co-investigators and Study teams at each participating center • Roper Hospital, Charleston, SC • University of Massachusetts Medical School, Worcester, MA • Levine Cancer Institute, Atrium Health, Charlotte NC • Miami Cancer In
Slide 17: Thank You
Thank You
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