Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — ASCO GU 2019
10 slides from Karyopharm Therapeutics's conference presentation, May 2019
Slide 1: Eltanexor (KPT-8602), a Second Generation SINE Compound, in mCRPC
Eltanexor (KPT-8602), a Second Generation Selective Inhibitor of Nuclear Export (SINE) Compound, in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) Jingsong Zhang1, David Chism2, Scot T. Tagawa3, Paul Monk4, Robert S. Alter5, William Reichmann6, William Senapedis6, Erkan Balogl
Slide 2: Background
Background ▪ Overexpression of exportin 1 (XPO1) in malignant cells increases the nuclear export / inactivation of tumor suppressor proteins (e.g. p53, IκB), and promotes the translation of Eukaryotic translation initiation factor 4E (eIF4E)-bound messenger ribonucleic acids (mRNA) coding oncoprotei
Slide 3: Preclinical Rationale
Preclinical Rationale 3 Aboukameel et al. Oncotarget, 2018, 9(82):35327
Slide 4: Study Design
Study Design This is part of a phase 1/2 study (NCT02649790) to determine the safety, preliminary efficacy, and recommended phase 2 dose (RP2D) of eltanexor in patients with advanced cancers. In this dose expansion cohort, patients with mCRPC received once daily oral eltanexor +/- Abi for 5 days per
Slide 5: Results
Results The dose escalation was completed in patients with Relapsed Refractory Multiple Myeloma (RRMM). The protocol defined Maximum Tolerated Dose (MTD) was not reached. The RP2D / schedule in RRMM was determined to be 20 mg of eltanexor + low dose dexamethasone / qdx5. The highest dose limiting to
Slide 6: Safety
Safety DLT Definition ▪ Grade ≥3 nausea/vomiting while on optimal supportive medication or any other Grade ≥3 non-hematological toxicity except alopecia or electrolyte abnormalities correctable with supportive therapy ▪ Grade 4 neutropenia >5 days; febrile neutropenia; Grade 4 thrombocytopenia; Grad
Slide 7: Efficacy
Efficacy Time on Treatment (ToT) for Evaluable Patients (As of 19-Nov-2018) 7
Slide 8: Efficacy
Efficacy Summary of Responses and Clinical Benefit ELTA (N=11) 1(9%) | 8(72%) | 5(45%) |2(18%)) 9(82%) 6 (55%) ELTA+ Abi(N=12) | 1(8%) | 9(75%) | 6 (50%) |2(17%)| 10 (83%) 7 (58%) Total (N=23) 2(9%) | 17 (74%) | 11 (48%) |4(17%)| 19 (83%) 13 (57%) Responses based on interim unaudited data (as of 19-
Slide 9: Efficacy
Efficacy Radiographic Progression Free Survival 100 Censored 75 Radiographic Progression Free Survival (rPFS) via RECIST v1.1 after at least 8 weeks PFS (%) 50 Note: PSA progression not used in this assessment ▪ Using Kaplan-Meier analysis, the median rPFS was 6.1 25 months (95% CI: 4.8, 8.4) among
Slide 10: Summary and Conclusions
Summary and Conclusions ▪ In this dose expansion cohort, patients with mCRPC received once daily oral eltanexor +/- abiraterone for 5 days per week (qdx5) at DLT cleared dose levels of 20 and 30 mg of eltanexor. ▪ Heavily pre-treated patients (median of 4 prior treatment regimens) with mCRPC whose d