|Phase 2b STORM Efficacy as of September 6, 2016|
|Category||N 1||ORR (%)||CBR (%)||VGPR (%)||PR (%)||MR (%)||SD (%)||PD (%)||NE (%)|
|Overall||78||16 (21%)||25 (32%)||4 (5%)||12 (15%)||9 (12%)||27 (35%)||9 (12%)||17 (22%)|
|Quad 2||48||10 (21%)||14 (29%)||2 (4%)||8 (17%)||4 (8%)||21 (44%)||4 (8%)||9 (19%)|
|Penta 3||30||6 (20%)||11 (37%)||2 (7%)||4 (13%)||5 (17%)||6 (20%)||5 (17%)||8 (27%)|
|1One patient not included, did not have active myeloma||ORR=Objective Response Rate (VGPR+PR)|
|2The majority of these patients (40 of 48) received 6 doses per cycle||CBR=Clinical Benefit Rate (VGPR+PR+MR)|
|3The majority of these patients (19 of 30) received 8 doses per cycle||VGPR=Very Good Partial Response|
Dr. Vogl said, "Patients with penta-refractory myeloma are no longer responding to any of our most effective myeloma agents. This is a growing population for whom we currently have no specific therapy, representing an unmet need. To my knowledge, selinexor is the first agent to show durable activity in this difficult-to-treat population. The results are particularly intriguing because the response rate to oral selinexor is comparable to that achieved with daratumumab or isatuximab. In addition, the overall survival seen in patients responding to selinexor is better than one would expect in this very refractory population. We look forward to further elucidating the potential benefits of selinexor in the STORM trial expansion, which will include approximately 120 additional patients with penta-refractory disease."To Karyopharm's knowledge, no agent has previously shown activity in patients with penta-refractory MM. As a result, the Company has expanded the STORM study to include approximately 120 additional patients with penta-refractory MM and expects to report top-line data from the expanded cohort in early 2018. Assuming a positive outcome, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM. Updated Phase 1b STOMP Clinical Data In an oral presentation titled, "Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory Multiple Myeloma Including Proteasome-Inhibitor Refractory Patients," Nizar Bahlis, MD, Associate Professor of Hematology, Southern Alberta Cancer Research Institute, will present updated clinical data from the selinexor + Velcade (bortezomib) + dexamethasone (SVd) arm of the ongoing Phase 1b/2 STOMP study in heavily pretreated relapsed/refractory MM patients. A summary of data from all 22 patients receiving selinexor in combination with Velcade and dexamethasone in the dose-escalation portion of the study treated as of July 25, 2016 is outlined in the following table and described below.
|Phase 1b STOMP Study (Selinexor + Velcade (Bortezomib) + Dexamethasone Arm) as of July 25, 2016|
|Prior PI Status||N||ORR (%)||CR (%)||VGPR (%)||PR (%)||MR (%)||SD (%)||PD (%)||CBR (%)|
|Refractory (7 Bortezomib, 3 Carfilzomib, 2 Ixazomib)||12||7 (58%)||1 (9%)||--||6 (50%)||3 (25%)||1 (68%)||1 (68%)||10 (83%)|
|Not Refractory (Exposed or Naïve)||10||10 (100%)||--||5 (50%)||5 (50%)||--||--||--||10 (100%)|
|All||22||17 (77%)||1 (5%)||5 (23%)||11 (50%)||3 (14%)||1 (5%)||1 (5%)||20 (91%)|
|ORR=Overall Response Rate (CR+VGPR+PR), CR=Complete Response, VGPR=Very Good Partial Response, PR=Partial Response, MR=Minor Response, SD=Stable Disease, PD=Progressive Disease|
The most commonly reported adverse events were fatigue, anorexia, nausea and diarrhea, which were primarily grade 1 or 2 and reversible. Four grade 3 and two grade 4 incidences of thrombocytopenia (without bleeding) were also reported. There was one reported case of grade 1 peripheral neuropathy in the selinexor (80 mg bi-weekly) cohort."We continue to be impressed with the high level of durable activity of selinexor in combination with bortezomib, especially in patients whose disease is already refractory to proteasome inhibitors," said Dr. Bahlis. "The tolerability profile of the combination was quite favorable with low rates of neuropathy and cytopenias, particularly in this heavily pretreated population. Selinexor appears to have one of the most potent synergistic effects with bortezomib reported to date." Based on the robust data from the SVd arm of the Phase 1b portion of the STOMP study, the Company plans to initiate a pivotal, randomized Phase 3 study, known as the BOSTON ( Bo rtezomib, S elinexor and dexame t has on e) study, which will evaluate SVd at the recommended dose compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. Karyopharm has identified the combination dose of selinexor (100mg weekly), bortezomib (1.3 mg/m2 weekly given sub-cutaneously for 4 of 5 weeks) and dexamethasone (40mg weekly) to be used in the BOSTON study. The study will be conducted worldwide and will enroll approximately 360 patients. Based on feedback from the FDA, the protocol is currently being finalized and the Company remains on track to commence the BOSTON study in early 2017. Dr. Bahlis continued, "To our knowledge, this is the only Phase 3 study evaluating a triple combination therapy incorporating once-weekly Velcade. We anticipate that this regimen will continue to show reduced rates of cytopenias, neuropathy and gastrointestinal side effects based on the continuing STOMP results. From a patient convenience as well as a health economic perspective, these data are very exciting because the combination of oral selinexor and bortezomib requires fewer doses and fewer hospital visits, making this treatment regimen much more patient friendly, and potentially more cost effective than currently established therapies."
In addition to these updated data from the STORM and STOMP studies, other key multiple myeloma abstracts selected for presentation at ASH include an oral presentation describing a Phase 1 study evaluating the combination of selinexor with proteasome inhibitor Kyprolis (carfilzomib) and dexamethasone in relapsed/refractory MM (Andrzej Jakubowiak, University of Chicago; Pub ID 973) and a poster presentation describing data from the selinexor + Pomalyst (pomalidomide) + dexamethasone arm of the Phase 1b dose-escalation portion of the STOMP study, also in patients with relapsed/refractory MM (Christine Chen, Princess Margaret Hospital; Pub ID 3330).Karyopharm to Host Multiple Myeloma-focused Dinner Reception and Webcast at ASH 2016 On Monday, December 5, 2016, Karyopharm will host an investor and analyst dinner reception, which will feature a moderated panel discussion with recognized thought leaders in the treatment of MM, updated selinexor data in MM, and a live Q&A session. The event will take place during the ASH 2016 annual meeting and interested parties can access a live webcast of the event beginning Monday, December 5, 2016 at 8:15 p.m. PT by going to the "Investors" section of the company's website at http://investors.karyopharm.com/events.cfm. Oral and Poster Presentations Highlighting Selinexor in Acute Myeloid Leukemia (AML) Several other key abstracts focused on the investigation of selinexor for the treatment of AML were selected for presentation at ASH, including two oral and two poster presentations. The first oral presentation describes updated data from the Phase 2 SAIL study evaluating the combination of selinexor, with Ara-C and Idarubicin in patients with relapsed/refractory AML (Walter Fiedler, University Medical Center Hamburg; Pub ID 341) and the second oral presentation highlights data from a clinical trial evaluating the combination of selinexor with high-dose cytarabine and mitoxantrone in patients with AML (Amy Wang, University of Chicago; Pub ID 212). The two poster presentations (Bhavana Bhatnagar, Ohio State University; Pub ID 1651 and Kendra Sweet, Moffitt Cancer Center, Tampa FL; Pub ID 4040) highlight early-stage clinical data demonstrating the feasibility and tolerability of selinexor in combination with other standard of care agents in patients with AML, including in elderly patients, as well as early signs of clinical activity, including response rates that are superior to historical data.
Details for the full list of ASH presentations are as follows:Oral presentations Title: Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study Presenter: Dan Vogl, Abramson Cancer Center, University of Pennsylvania Publication ID: 491 Session: 653. Myeloma: Therapy, excluding Transplantation: New Agents for Multiple Myeloma; Sunday, December 4, 2016; 4:30-6:00 PM PT Location: San Diego Convention Center, Hall AB Date and Time: Sunday, December 4, 2016 at 5:30 PM PT Title: Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory MM Including Proteasome-Inhibitor Refractory Patients Presenter: Nizar Bahlis, Southern Alberta Cancer Research Institute, University of Calgary Publication ID: 977 Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT Location: Manchester Grand Hyatt San Diego, Seaport Ballroom BC Date and Time: Monday, December 5, 2016; 3:45 PM PT Title: Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and Dexamethasone in Relapsed/Refractory MM Presenter: Andrzej Jakubowiak, University of Chicago Publication ID: 973 Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT Location: Manchester Grand Hyatt San Diego, Seaport Ballroom BC Date and Time: Monday, December 5, 2016; 2:45 PM PT Title: Phase II Results of Ara-C and Idarubicin in Combination with the Selective Inhibitor of Nuclear Export Compound Selinexor in Patients with Relapsed or Refractory AML Presenter: Walter Fiedler, University Medical Center Hamburg, Hamburg, Germany Publication ID: 341 Session: 613. Acute Myeloid Leukemia: Clinical Studies: Optimizing Current AML Therapy; Sunday, December 4, 2016; 9:30-11:00 AM PT Location: Marriott Marquis San Diego Marina, Pacific Ballroom Date and Time: Sunday, December 4, 2016; 10:30 AM PT Title: Combination of Selinexor with High-Dose Cytarabine and Mitoxantrone for Remission Induction in AML Is Feasible and Tolerable Presenter: Amy Wang, University of Chicago Publication ID: 212 Session: 613. Acute Myeloid Leukemia: Clinical Studies: Innovations in Induction Therapy; Saturday, December 3, 2016; 4:00-5:30 PM PT Location: Marriott Marquis San Diego Marina, San Diego Ballroom AB Date and Time: Saturday, December 3, 2016; 4:15 PM PT Title: Selective Inhibition of Nuclear Cytoplasmic Transport as a New Treatment Paradigm in Myelofibrosis Presenter: Dongqing Yan, Huntsman Cancer Institute, University of Utah Publication ID: 636 Session: 635. Myeloproliferative Syndromes: Basic Science: Translational Studies; Monday, December 5, 2016; 7:00-8:30 AM PT Location: Marriott Marquis San Diego Marina, Pacific Ballroom Salons 15-17 Date and Time: Monday, December 5, 2016; 8:15 AM PT Title: XPO1 Inhibition By Selinexor Synergizes with BCR Inhibition, Blocks Tumor Growth and Prolongs Survival in a Bioluminescent Animal Model of Primary Central Nervous System Lymphoma Presenter: Marta Crespo, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain Publication ID: 463 Session: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Novel Therapeutic Strategies Location: San Diego Convention Center, Room 5AB Date and Time: Sunday, December 4, 2016; 4:30 PM PT Title: The mechanism by which mutant NPM1 creates Leukemic self-renewal is readily reversed Presenter: Yogen Saunthararajah, Cleveland Clinic and Case Comprehensive Cancer Center, Cleveland, OH Publication ID: 444 Session: 603. Oncogenes and Tumor Suppressors: Transcriptional Networks Contributing to Leukemogenesis Location: San Diego Convention Center, Room 6DE Date and Time: Sunday, December 4, 2016; 5:45 PM PT Title: Bromodomain and Extra-Terminal Motif Proteins (BETs) Mediate 5-Azacitidine Resistance in Myeloid Leukemia through Recruitment of an Active RNA Polymerase II Complex Presenter: Li Chen, University of Chicago Publication ID: 746 Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Novel Epigenetic Modulators Location: San Diego Convention Center, Room 24 Date and Time: Monday, December 5, 2016; 10:45 AM PT Poster presentations Title: Selinexor Shows Synergy in Combination with Pomalidomide and Low Dose Dexamethasone in Patients with Relapsed / Refractory Multiple Myeloma Presenter: Christine Chen, Princess Margaret Hospital, Toronto, ON Publication ID: 3330 Location: San Diego Convention Center, Hall GH Date and Time: Sunday, December 4, 2016; 6:00-8:00 PM PT Title: A Phase 1 Clinical Trial of Selinexor in Combination with Decitabine in Patients with Newly Diagnosed and Relapsed or Refractory AML Presenter: Bhavana Bhatnagar, Ohio State University Publication ID: 1651 Location: San Diego Convention Center, Hall GH Date and Time: Saturday, December 3, 2016; 5:30-7:30 PM PT Title: A Phase I Study of Selinexor in Combination with Daunorubicin and Cytarabine in Patients with Newly Diagnosed Poor-Risk AML Presenter: Kendra Sweet, Moffitt Cancer Center, Tampa FL Publication ID: 4040 Location: San Diego Convention Center, Hall GH Date and Time: Monday, December 5, 2016; 6:00-8:00 PM PT Title: A Phase 1/2 Study of the Second Generation Selective Inhibitor of Nuclear Export Compound, KPT-8602, in Patients with Relapsed Refractory MM Presenter: Frank Cornell, Vanderbilt Ingram Cancer Center, Nashville; TN Publication ID: 4509 Location: San Diego Convention Center, Hall GH Date and Time: Monday, December 5, 2016; 6:00-8:00 PM PT Title: Combination of Selective Inhibitor of Nuclear Export Compounds, Selinexor and KPT-8602, with Venetoclax (ABT-199) Displays Enhanced Activity in Leukemia and Large Cell Lymphoma Presenter: Melissa Fischer, Vanderbilt University, Nashville, TN Publication ID: 3949 Location: San Diego Convention Center, Hall GH Date and Time: Monday, December 5, 2016; 6:00-8:00 PM PT Title: Synergistic anti-tumor effects of KPT-8602 and Panobinostat a pan-HDAC inhibitor in multiple myeloma Presenter: Christian Argueta, Karyopharm Therapeutics, Newton, MA Publication ID: 3298 Location: San Diego Convention Center, Hall GH Date and Time: Sunday, December 4, 2016; 6:00-8:00 PM PT Title: Selinexor in combination with chemotherapy or Idelalisib elicits a synergistic cytotoxic effect in Primary CLL Cells and overcoming intrinsic and stromal cells-mediated Fludarabine resistance Presenter: Marta Coscia, A.O.U. Città della Salute e della Scienza, University of Torino, Torino, Italy Publication ID: 3210 Location: San Diego Convention Center, Hall GH Date and Time: Sunday, December 4, 2016; 6:00-8:00 PM PT Title: Combination therapy with Bortezomib or Carfilzomib and Selinexor Induces Nuclear Localization of I¿Ba and overcomes acquired proteasome inhibitor Resistance in Human Multiple Myeloma Presenter: Joel Turner, Moffitt Cancer Center, Tampa FL Publication ID: 3299 Location: San Diego Convention Center, Hall GH Date and Time: Sunday, December 4, 2016; 6:00-8:00 PM PT Title: Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T Cell Effector Function in Mice: Implications for Combination with Immunotherapy Presenter: Yosef Landesman, Karyopharm Therapeutics, Newton, MA Publication ID: 2525 Location: San Diego Convention Center, Hall GH Date and Time: Sunday, December 4, 2016; 6:00-8:00 PM PT Title: Combination of selinexor and the proteasome inhibitor, bortezomib shows synergistic cytotoxicity in Diffuse Large B-Cells Lymphoma Cells In vitro and in vivo Presenter: Trinayan Kashyap, Karyopharm Therapeutics, Newton, MA Publication ID: 4131 Location: San Diego Convention Center, Hall GH Date and Time: Monday, December 5, 2016; 6:00-8:00 PM PT Title: XPO1 target occupancy measurements using Fluorescence Cross Correlation Spectroscopy (FCCS) support the Selinexor Recommended Phase 2 Dose Presenter: Marsha Crochiere, Karyopharm Therapeutics, Newton, MA Publication ID: 1563 Location: San Diego Convention Center, Hall GH Date and Time: Saturday, December 3, 2016; 5:30-7:30 PM PT Title: Identification of Specific HnRNPs as Novel Therapeutic Targets and Responsive Indicators of KPT330 (selinexor) in Leukemia Presenter: Adam Cloe, University of Chicago Publication ID: 1657 Location: San Diego Convention Center, Hall GH Date and Time: Saturday, December 3, 2016; 5:30-7:30 PM PT 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 1,800 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 combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in acute myeloid leukemia (SOPRA), diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in early 2017. 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 the Company's clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov. About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent and combination activity against a variety of human cancers, SINE™ compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330), will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended June 30, 2016, which was filed with the Securities and Exchange Commission (SEC) on August 4, 2016, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Velcade® is a registered trademark of Takeda Pharmaceutical Company LimitedRevlimid® and Pomalyst® are registered trademarks of Celgene CorporationKyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc.Darzalex™ is a trademark of Janssen Biotech, Inc.
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