Slide 1: Open-Label Study of Diarrhea in Early-Stage HER2+ Breast Cancer with Neratinib and Loperamide
An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide Prophylaxis
Slide 2: Diarrhea in ExteNET Trial
Diarrhea in ExteNET Trial 1.0 Diarrhea grade 0.8 3 0.6 Incidence 0.4 0.2 0.0 1 2 3 4 5 6 7 8 9 10 11 12 Study time (months) Pts with events 1310 692 615 569 513 490 453 413 437 414 392 366 Pts at risk 1408 1146 1074 1033 1006 971 935 924 911 888 873 863 Diarrhea* 95.4% All Grade (Grade 1-4) diarrhea
Slide 3: Neratinib-Diarrhea Prophylaxis with Loperamide in Metastatic Cancer
Neratinib-Diarrhea Prophylaxis with Loperamide in Metastatic Cancer
Slide 4: Phase II Open-Label Study of Diarrhea with Neratinib and Loperamide Prophylaxis
Phase II Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide Prophylaxis Goal: Investigate the use of loperamide given prophylactically to reduce neratinib related diarrhea in patient
Slide 5: Study Schema and Status
Study Schema and Status Patients enter study within 1 year of completing adjuvant trastuzumab therapy (analogous to ExteNET population) Other prior HER2+ (neo) adjuvant therapy is permitted Early HER2+ Breast Cancer Received up to 1 year of adjuvant trastuzumab Stage I-3c HR (ER/PR) positive or nega
Slide 6: Dosing Regimens
Dosing Regimens Original Protocol (n=27) Day 1 : 16 mg/day (4 mg starting dose + 4 mg tid) Days 2-3: 12 mg/day (4 mg tid) Days 4-56 : 6-8mg/day (2 mg tid or qid) Amended Protocol (n=23) Days 1-14: 12 mg/day (4 mg tid) Day 15-56: 8 mg/day (4 mg bid)
Slide 7: Study Preliminary Results
Study Preliminary Results Copyright 2015 Puma Biotechnology
Slide 8: Patient Characteristics
Patient Characteristics Original Protocol Amendment 1 Total (N=27)(N=23)(N=50) Hormone receptor 23 (85.2%) 13 (56.5%) 36 (72%) positive (ER/PR+) Hormone receptor 4 (14.8%) 10 (43.5%) 14 (28%) negative (ER/PR-)
Slide 9: Incidence of Grade Treatment-emergent Diarrhea
Incidence of Grade 3 Treatment-emergent Diarrhea Original Protocol Amendment 1 Total (N=27)(N=23)(N=50) Patients with events—n (%) Grade 3 Diarrhea 5 (18.5) 3 (13.0) 8 (16.0) Incidence of Grade 3 18.5% (6.3, 38.1) 13.0% (2.8, 33.6) 16.0% (7.2, 29.1) Diarrhea (95% CI) Non Compliant with Loperamide 3/
Slide 10: Characteristics of Treatment-emergent Diarrhea
Characteristics of Treatment-emergent Diarrhea Original Protocol Amendment 1 Total (N=27)(N=23)(N=50) Any Grade – n (%) 20 (74.1) 10 (43.5) 30 (60.0) Grade 3 5 (18.5) 3 (13.0) 8 (16.0) Hospitalizations 0 (0.0) 0 (0.0) 0 (0.0) Action taken – n (%) Anti-diarrheal 9 (33.3) 6 (26.1) 15 (30.0) medication
Slide 11: Chemotherapy Regimens and Targeted Agents Commonly Associated With Diarrhea
‘TABLE 1, Chemotherapy Regimens and Targeted Agents Commonly Associated With Diarrhea, Data From Randomized Controlled Trials ett «a | tin 1s : Lapa 7 [zo ile [es in 21 Laat eapestabne 6 rm 7 Capscabine + docetne I [2s Olptospromie, metabo + ‘ ™ Smcrurac | i Peruzuna,Wastizumat, docetnl + | 72 2 [es
Slide 12: Treatment-emergent Diarrhea by Treatment Cycle
Treatment-emergent Diarrhea by Treatment Cycle W = week C = cycle
Slide 13: Duration of Treatment-emergent Diarrhea
Duration of Treatment-emergent Diarrhea Original Protocol Amendment 1 Total (N=27)(N=23)(N=50) Duration of any grade (grade 1-3) diarrhea (days) Median 3.0 3.0 3.0 Duration of grade 3 diarrhea (days) Median 1.0 2.0 2.0
Slide 14: Summary of Findings
Summary of Findings Based on preliminary results in patients receiving loperamide prophylaxis, the estimated frequency of all grade diarrhea is 60% and grade 3 diarrhea is 16% - Estimated frequency of all grade diarrhea for original protocol is 74.1% and grade 3 diarrhea is 18.5% - Estimated frequen
Slide 15: Future Plans
Future Plans Continue following additional patients in Amendment 1 cohort Report additional results (n=72) in 2016