Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — Technical Presentation (December 2021)
16 slides from Karyopharm Therapeutics's technical presentation, Dec 1, 2021
Slide 1: A Phase II Study of Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL)
A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in Patients with Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL study) Srinivas K. Tantravahi1, MBBS, Soo Jin Kim1, MS, Divya Sundar1, Ami B. Patel1, MD, Anthony D. Pomicter1, MS, Kenneth M. Boucher2, PhD, Kama
Slide 2: Disclosures
Disclosures Honoraria: Karyopharm Therapeutics Inc., Novartis Research Funding: Karyopharm Therapeutics Inc; Research Funding: BMS; Novartis; CTI BioPharma; Abbvie Inc. (Institutional support) Consultancy: Karyopharm Therapeutics Inc., Novartis 2
Slide 3: Background: Nuclear–Cytoplasmic Transport is a Novel Therapeutic Target in Myelofibrosis
Background: Nuclear–Cytoplasmic Transport (NCT) is a Novel Therapeutic Target in Myelofibrosis (MF) • JAK inhibitors (JAKi), ruxolitinib and fedratinib reduce spleen volume, alleviate constitutional symptoms and improve quality of life in MF patients • However, some patients demonstrate inadequate r
Slide 4: ESSENTIAL Study Design
ESSENTIAL Study Design Primary Endpoint • Spleen volume response defined Myelofibrosis as ≥35% reduction by MRI or CT of the resistant (at least 3 Low Dose Oral abdomen after week 24 of selinexor months of JAKi Selinexor treatment treatment) or 60 - 80 mg QW intolerant to JAKi Key Secondary Endpoint
Slide 5: Key Eligibility Criteria
Key Eligibility Criteria • Diagnosis of primary MF, post-essential thrombocytosis MF, or post-polycythemia-vera MF • Prior treatment with JAKi with any of the following: – Resistance to JAKi after ≥ 3 months of treatment: palpable spleen > 10 cm OR palpable spleen > 5 cm with active symptoms of MF –
Slide 6: ESSENTIAL Baseline Demographics
ESSENTIAL Baseline Demographics ID Driver Addi�onal Prior treatments Dura�on of prior JAKi • Between May 2019 and February 2021, 12 muta�on muta�ons JAKi therapy refractory or patients (pts) enrolled (7 men and 5 women) (months) intolerant • Median age 68 years (range 43 to 80) 01-001 JAK2 ASXL1, U2
Slide 7: Single Agent Selinexor resulted in robust SVR35 rate of 40% at ≥24 weeks
Single Agent Selinexor resulted in robust SVR35 rate of 40% at ≥24 weeks in MF resistant or intolerant to JAKi % Spleen volume change (%) 40 30 27% Week 12 20 Week 24 10 Week >24 2% 0 -3% -2.5% -10 Ongoing -20 SVR25 -30 -25% -32% Ongoing SVR35 -40 -37% -43% • Two patients not evaluable: One patient
Slide 8: Hemoglobin improvement observed in patients with hemoglobin <10 g/dL
Hemoglobin improvement is observed in 4 out of 8 pts with hemoglobin < 10 g/dL at screening Patient Baseline Best response Transfusion requirements 01-001 TD Became TI 01-003 TD (<6u/ 12 weeks) Became TI TD to TI occurred in 40% (2 out of 5) 01-004 TD Unchanged 01-010 TD Unchanged 01-011 TD Unchange
Slide 9: Swimmers Plot: Durable responses with long term therapy beyond 2 years
Swimmers Plot: Durable responses with long term therapy beyond 2 years 001 Off Treatment 003 60 mg 004 Off Treatment 005 40 mg Median treatment 006 duration 11 months Individual Patients Death 007 Off Treatment [range 2.8 to 28.8 008 Off Treatment months] 009 Off Treatment 010 60 mg 011 Off Treatmen
Slide 10: Overall Survival Status: current 2-year survival probability is 91.7%
Overall Survival Status: current 2-year survival probability is 91.7% Median OS not reached after a median follow up of 11.1 months [range 3 to 30 months]. The 2-year survival probability is 91.7%
Slide 11: Selinexor treatment resulted in rapid decrease of total WBC and LDH concentrations
Selinexor treatment resulted in rapid decrease of total WBC and LDH concentrations WBC LDH 60 2000 1800 50 1600 1400 40 1200 k/uL U/L 30 1000 800 20 600 400 10 200 0 0 TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP TP 1 TP 2 TP 3 TP 4 TP 5 TP 6 TP 7 TP 8 TP
Slide 12: MPN-SAF symptom score changes on selinexor
MPN-SAF symptom score changes on selinexor Patient Score at screening Best response 01-001 66 7 01-004 4 30 01-005 30 15 01-007 28 30 01-009 14 11 01-011 22 10 01-012 70 39 01-013 28 18 Patient 003, 006, 008 excluded due to missing TSS score at baseline. Patient 10 excluded due to score 0 at baselin
Slide 13: Safety
Safety Treatment Emergent Adverse Selinexor 80 or 60 mg weekly Events1 (N = 12) Non-Hematologic Grade 1-2 Grade 3 and 4 Grade 5 Weight loss 3 (25%) 1 (8%) - Fatigue 4 (33%) 4 (33%) - Dyspnea and Hypoxia 1 (8%) 2 (17%) - Hypertension - 2 (17%) - Dizziness 3 (25%) 2 (17%) - Flu like symptoms 2 (17%) 2
Slide 14: Reduction in marrow fibrosis at long term follow up supports potential disease modification
Reduction in marrow fibrosis at long term follow up supports potential disease modification • Reduction in marrow reticulin fibrosis 001-005: Reticulin Fibrosis (reticulin special stain, 200X) from MF grade 3 to MF grade 1 at week 72 (patient 001-005) Screening Week 24 Week 72 • No change in marrow
Slide 15: Plasma inflammatory cytokines
Plasma inflammatory cytokines Box plots demonstrating concentrations of representative cytokines at screening and during selinexor treatment. Higher concentrations of cytokines were observed in pt 001-009 (yellow circle) who had progressive disease at week 12. 15
Slide 16: Conclusions
Conclusions • Once weekly, low dose oral selinexor demonstrated robust single agent activity with sustained spleen responses in JAKi refractory MF • Responses were durable with long term therapy beyond 2 years • Improvement in anemia and symptom scores were observed • Promising overall survival (med
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