On March 19, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that eight posters will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting taking place April 14-18, 2018 in Chicago (Press release, Karyopharm, MAR 19, 2018, View Source [SID1234525409]).The eight poster presentations will feature preclinical data for the Company’s lead, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor, its second-generation oral SINE compound eltanexor, and its pipeline asset KPT-9274, an oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT).
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Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm commented, "Collectively, the data being presented at AACR (Free AACR Whitepaper) this year continue to provide important insights that will help guide the future clinical development of selinexor, eltanexor and KPT-9274 across a wide range of malignancies, both as single agents and in combination."
Details of each of the presentations are provided below:
Selinexor
Galinski et al. show that the combination of selinexor with bortezomib (SV) is synergistic and reduces the activity of nuclear factor kappa-B (NFkB) in aggressive neuroblastoma cell lines. These results further support observed synergies driving Karyopharm’s ongoing Phase 3 "BOSTON" study of SV plus low dose dexamethasone (SVd) versus Vd, which is being studied in patients with relapsed myeloma. Furthermore, these results may lead to additional applications of the SV and/or SVd combination regimens.
Title:Combination Treatment with Selinexor and Bortezomib for Management of Highly Aggressive Neuroblastoma
Presenter: Basia Galinski, Albert Einstein College of Medicine
Poster Board #: 3193/25
Session: PO.TB08.02 – Pediatrics 2: Preclinical Therapies, Resistance, and Stem Cells
Location: Section 7
Date and Time:Tuesday, April 17, 2018; 8:00 AM – 12:00 PM CT
Chang et al. show that the combination of selinexor with the PARP inhibitor Zejula (niraparib) provide enhanced efficacy over either agent alone in preclinical models of ovarian cancer. These results support the previously reported activity of single agent selinexor in patients with ovarian and endometrial cancers in the SIGN study (ESMO, 2017), as well as the ongoing combination of selinexor with the PARP inhibitor Lynparza (olaparib) in an investigator-sponsored study at the MD Anderson Cancer Center in Houston, Texas. Furthermore, based on these data, selinexor combinations with additional PARP inhibitors are being considered.
Title:Enhanced Anti-Tumor Effects of Selinexor and Niraparib in Preclinical Models of Ovarian Cancer
Presenter: Hua Chang, Karyopharm Therapeutics, Inc.
Poster Board #: 5826/22
Session: PO.ET01.04 – Combination Chemotherapy 2
Location: Section 37
Date and Time:Wednesday, April 18, 2018; 8:00 AM – 12:00 PM CT
Wahbe et al. show that selinexor has activity against glioblastoma multiforme (GBM) cells in vitro and in vivo, supporting the previously reported and ongoing study of single agent selinexor in recurrent GBM in clinical study KING. These data also support planned investigator-sponsored studies of selinexor in combination with radiation and/or other DNA-damaging agents in this indication.
Title:The XPO1 Inhibitor Selinexor Attenuates Global Translation and Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and In Vivo
Presenter:Amy Wahba, National Cancer Institute
Poster Board #: 4444/11
Session: PO.MCB04.04 – Post-transcriptional and Translational Control of Cell Fate
Location: Section 21
Date and Time:Tuesday, April 17, 2018; 1:00 PM – 5:00 PM CT
Additional preclinical studies with selinexor support the potential for the agent in hormone receptor positive breast cancer as well as in gastric cancer.
Title:Combined Targeting of Estrogen Receptor Alpha and Nuclear Transport Pathways Remodel Metabolic Pathways to Induce Autophagy and Overcome Endocrine Resistance
Presenter:Zeynep Madak Erdogan, University of Illinois at Urbana-Champaign
Poster Board #: 3733/3
Session: PO.EN01.02 – Steroid Receptors and Preclinical Studies of Endocrine-Related Cancers
Location: Section 31
Date and Time:Tuesday, April 17, 2018; 8:00 AM – 12:00 PM CT
Title:Nuclear Exporter Protein XPO1 a Novel Prognostic and Therapeutic Target in Gastric Cancer
Presenter: Irfana Muqbil, University of Detroit Mercy
Poster Board #: 2491/12
Session: PO.MCB03.03 – Nuclear Oncoproteins and Tumor Suppressor Genes
Location: Section 21
Date and Time:Monday, April 16, 2018; 1:00 PM – 5:00 PM CT
Eltanexor
Preclinical studies with eltanexor support the rationale for Karyopharm’s ongoing single-agent study of eltanexor in multiple indications including castration-resistant prostate cancer (CRPC) and myelodysplastic syndromes (MDS), as well as in potential future combinations of eltanexor in CRPC, MDS or acute myeloid leukemias (AML).
Title:Selective Inhibitor of Nuclear Export (SINE) Compound, Eltanexor (KPT-8602), Synergizes with Venetoclax (ABT-199) to Eliminate Leukemia Cells and Extend Survival in an In Vivo Model of Acute Myeloid Leukemia
Presenter:Melissa A. Fischer, Vanderbilt University School of Medicine
Poster Board #: 1877/8
Session: PO.ET06.04 – Experimental Agents and Combinations for Hematologic Malignancies 2
Location: Section 38
Date and Time:Monday, April 16, 2018; 8:00 AM – 12:00 PM CT
Title:Down-Regulation of AR Splice Variants Through XPO1 Suppression Contributes to the Inhibition of Prostate Cancer Progression
Presenter: Irfana Muqbil, University of Detroit Mercy
Poster Board #: 2492/13
Session: PO.MCB03.03 – Nuclear Oncoproteins and Tumor Suppressor Genes
Location: Section 21
Date and Time:Monday, April 16, 2018; 1:00 PM – 5:00 PM CT
KPT-9274
Mpilla et al. demonstrate that PAK4-NAMPT dual inhibition with KPT-9274 has activity in preclinical models of resistant pancreatic neuroendocrine tumors.
Title:PAK4-NAMPT Dual Inhibition as a Feasible Strategy for Treatment of Resistant Pancreatic Neuroendocrine Tumors
Presenter: Gabriel Mpilla, Wayne State University School of Medicine
Poster Board #: 4368/10
Session: PO.MCB01.01 – GTPases and Their Regulators and Effectors
Location: Section 17
Date and Time:Tuesday, April 17, 2018; 1:00 PM – 5:00 PM CT
About Selinexor
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,200 patients have been treated with selinexor, and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.