3. Pardanani A, et al. Leukemia 2009;23: Hedvat M, et al. Cancer Cell 2009;16:

Transcription

1 A Phase / Study of NS-8, an Oral JAK Inhibitor, in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (ppv MF), or Post-Essential Thrombocythemia Myelofibrosis (pet MF) 8 Srdan Verstovsek, MD PhD, Moshe Talpaz, MD, Ellen Ritchie, MD, Martha Wadleigh, MD, Olatoyosi M Odenike, MD, 5 Catriona Jamieson, MD PhD, Brady Stein, MD, 7 Tomonori Uno, PhD, 8 Ruben A Mesa, MD. 9 Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI; Cornell University, New York, NY; Dana-Farber Cancer Institute, Boston, MA; 5 University of Chicago Medical Center, Chicago, IL; Division of Regenerative Medicine, University of California, San Diego, CA; 7 Northwestern University, Feinberg School of Medicine, Chicago, IL; 8 NS Pharma, Inc., Parsippany, NJ; 9 Mayo Clinic, QR CODE TABLE. NS-8 is a potent and specific inhibitor of JAK. Compound JAK inhibition (IC 5, nm) Other kinase inhibition (IC 5, nm) vs JAK vs JAK vs TYK vs Flt vs c-src NS < Ruxolitinib.5.7 Momelotinib 8 55 AZD8 <...9 Fedratinib Pacritinib Nakaya Y, et al. Blood Cancer J ;:e9.. Williams WV, et al. Ann Rheum Dis 8;7.. Pardanani A, et al. Leukemia 9;: 5.. Hedvat M, et al. Cancer Cell 9;: Wernig G, et al. Cancer Cell 8:.. Hart S, et al.leukemia ;5:75 9. Poster 8 Presented at the 57th ASH Annual Meeting and Exposition, December 5 8, 5, Orange County Convention Center, Orlando, FL

2 QR CODE TABLE. Baseline demographics of patient population. 75 mg 5 mg mg mg mg mg mg 5 mg mg mg Number of patients Median age, years (range) (7 7) (5 8) (9 7) (5 77) ( 7) (55 7) ( 7) (8 7) ( 8) (5 79) Male/female, n / / / / / / / 5/ / 5/ MF classification, n PMF Post-PV/MF Post-ET/MF ECOG PS, n 7 5 Median spleen size, cm (range) (9) ( ) (.5) ( ) (9 ) ( 7) ( 5) ( ) (8 ) (9 ) JAK mutation, n JAKV7F positive JAKV7F negative, twice-daily dosing; ECOG PS, Eastern Cooperative Oncology Group performance status; ET, essential thrombocytopenia; MF, myelofibrosis; PMF, primary MF; PV, polycythemia vera;, once-daily dosing. Poster 8 Presented at the 57th ASH Annual Meeting and Exposition, December 5 8, 5, Orange County Convention Center, Orlando, FL

3 QR CODE TABLE. Drug-related AEs observed in > patients. N (%), all grades / N (%), grade / 75 mg (n=) 5 mg (n=) mg (n=9) mg mg Ph (n=) Ph (n=) (n=) mg (n=5) mg (n=) 5 mg (n=8) mg (n=) mg (n=8) Any AE ()/ () / 5 (7)/ (9)/5 () 5 ()/ ()/ (5)/ (5) (5)/ 5 ()/ (8) 9 (75)/ () 7 (88)/ (8) Hematologic AEs Thrombocytopenia a Anemia a ()/ () ()/ (9)/ (9) ()/ (5)/ ()/ () (8)/ (8)/ () ()/ ()/ (8) (7)/ (7) ()/ () (5)/ () Non-hematologic AEs Dizziness Nausea Diarrhea Paresthesia Weight increased Headache Vomiting Esophageal reflux ()/ ()/ ()/ ()/ (9)/ () ()/ ()/ ()/ ()/ ()/ (8)/ (8)/ (5)/ (5)/ (5)/ (5)/ (5)/ (8)/ (8)/ ()/ ()/ () (5)/ () ()/ (5)/ ()/ (8)/ (7)/ (8) (8)/ (8)/ (5)/ () ()/ ()/ N includes patients in the original dose cohort, or who were dose escalated or reduced to that cohort. a 75 mg : grade thrombocytopenia (n=). mg : grade anemia (n=). mg : grade thrombocytopenia (n=); grade thrombocytopenia (n=); grade anemia (n=). mg : grade anemia (n=). mg : grade thrombocytopenia (n=). mg : grade thrombocytopenia (n=). 5 mg : grade thrombocytopenia (n=); grade thrombocytopenia (n=); grade anemia (n=). mg : grade thrombocytopenia (n=); grade thrombocytopenia (n=); grade thrombocytopenia (n=); grade anemia (n=). mg : grade thrombocytopenia (n=); grade anemia (n=); grade anemia (n=). AE, adverse event;, twice-daily dosing;, once-daily dosing. Poster 8 Presented at the 57th ASH Annual Meeting and Exposition, December 5 8, 5, Orange County Convention Center, Orlando, FL

4 QR CODE TABLE. Clinical response. Splenic reductions 5%, n/n (%) a Median cycles (range) to splenic reductions 5% % Splenic reductions, n/n (%) a Splenic clinical improvement, n/n (%) a,b Hb/Plt clinical improvement, n/n (%) b,c All doses / (5) ( ) / () / () Hb: / () Plt: / () 75 mg / () / () / () 5 mg / () / () Plt: / (5) mg /5 () /5 () /5 () / () mg 5/9 (5) ( 8) 5/9 (5) /9 () Hb: /9 () mg / () / () / () / () mg / () 7.5 ( ) / () / () Hb: / () mg / () / () / () / () 5 mg / (5) / (5) / () / () mg / (5) / (5) / () Hb: /7 () mg / (7).5 ( ) / (7) / (7) / () Prior JAKi treatment 9/9 (7) ( ) 5/9 () /9 () Hb: /8 (7) Plt: /8 () a Assessed in evaluable patients: baseline splenomegaly 5 cm and treatment for cycle. b All measures of clinical improvement had to be confirmed for 8 weeks. c Assessed in patients who had received cycle of treatment., twice-daily dosing; Hb, hemoglobin; JAKi, JAK inhibitor; Plt, platelet;, once-daily dosing. Poster 8 Presented at the 57th ASH Annual Meeting and Exposition, December 5 8, 5, Orange County Convention Center, Orlando, FL

5 QR CODE FIGURE. Systemic exposure of NS-8. (A) Plot of plasma concentration of NS-8 over time on Day 8. (B) AUC of NS-8 on Day 8. (A) 75 mg mg 5 mg mg mg 5 mg mg mg mg mg Mean plasma concentration (ng/ml) Anti-proliferative activity; 5 ng/ml 5 7 Time post-dose (h) 8 (B) Dose () Mean AUC (ng/ml hr) CV% 75 mg mg 9 mg 88 mg 8 mg Dose () Mean AUC (ng/ml hr) CV% mg 8 9 mg mg 9 mg 7 mg 99 5 AUC, area under the plasma concentration time curve over hours;, twice-daily dosing; CV, coefficient of variation;, once-daily dosing. Poster 8 Presented at the 57th ASH Annual Meeting and Exposition, December 5 8, 5, Orange County Convention Center, Orlando, FL 5