On March 15, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the fourth quarter and full year 2017 and provided an overview of recent accomplishments and clinical development plans for selinexor, its lead, novel, oral SINE compound, and eltanexor, its second-generation oral SINE compound Karyopharm Therapeutics Inc. (Nasdaq:KPTI), (Press release, Karyopharm, MAR 15, 2018, View Source [SID1234524794]).
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"2017 was a year of significant achievement for Karyopharm where we reported positive clinical data from our lead selinexor programs, including the Phase 1b/2 STOMP study in multiple myeloma (MM), the Phase 2b SADAL study in diffuse large B-cell lymphoma (DLBCL), and the Phase 2/3 SEAL study in liposarcoma, and the subsequent advancement of each study," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are looking forward to an event-driven 2018 beginning at the end of April with top-line results from the Phase 2b STORM study, followed by top-line data from the Phase 2b SADAL study by the year end. Assuming positive outcomes, we plan to use the data from both of these studies to support requests for accelerated approval from the U.S. Food and Drug Administration (FDA) and conditional approval from the European Medicines Agency (EMA) in these indications. On the corporate front, we continue to build out our commercial team in anticipation of a potential selinexor launch in the U.S. in 2019."
Fourth Quarter 2017 and Recent Events
New Strategic Relationships
Biogen’s Acquisition of KPT-350 for the Treatment of Neurological and Neurodegenerative Diseases. In January 2018, Karyopharm announced its entry into an agreement with Biogen to acquire Karyopharm’s investigational oral SINE compound KPT-350 targeting certain neurological and neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS). The transaction carries a total deal value of up to $217 million, plus royalties.
Exclusive License Agreement with Ono Pharmaceutical Co., Ltd. (Ono) to Develop and Commercialize Selinexor and Eltanexor in Japan and Other Countries in Asia. In October 2017, Karyopharm announced its entry into an exclusive license agreement with Ono for the development and commercialization of selinexor and eltanexor. The agreement includes the development of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in Japan, South Korea, Taiwan, Hong Kong, and the ASEAN countries (the Territory). The transaction carries a total deal value of up to $193.0 million based on the exchange rate on the effective date of the license agreement plus royalties. Karyopharm retains all rights to selinexor and eltanexor outside the Territory.
Selinexor in Multiple Myeloma
Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. Karyopharm expects to report top-line data from the expanded STORM study cohort at the end of April 2018, and, assuming a positive outcome, intends to use the data from this study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor for penta-refractory MM. The Phase 2b STORM study was previously expanded to include 122 additional patients with penta-refractory MM.
Pivotal Phase 3 BOSTON Study Underway. Karyopharm’s pivotal, randomized Phase 3 BOSTON (Bortezomib, Selinexor and dexamethasone) study is now underway and enrolling patients in 14 countries globally. BOSTON is designed to evaluate 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and dexamethasone (SVd), compared to standard twice weekly Velcade and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The primary endpoints of the study are progression free survival and overall response rate. Both the trial design and endpoints have been agreed to by the FDA and the EMA as acceptable to support an application for approval. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and is expecting completion of enrollment in 2018, with top-line data anticipated in 2019.
Positive Phase 1b/2 STOMP Data Presented at ASH (Free ASH Whitepaper) 2017. Data presentations featuring clinical results from four treatment arms of the ongoing Phase 1b/2 STOMP study evaluating selinexor in combination with standard therapies for the treatment of patients with MM were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting (ASH 2017). Collectively, the STOMP study data presented at ASH (Free ASH Whitepaper) 2017 continue to provide evidence of tolerability and robust anti-myeloma activity when selinexor is combined with the currently available standard myeloma therapies, including proteasome inhibitors including Velcade, immunomodulatory drugs and anti-CD38 monoclonal antibodies. Additional treatment arms with selinexor in patients with newly diagnosed disease in combination with lenalidomide, and in combination with the proteasome inhibitor Kyprolis (carfilzomib) have been added.
Selinexor in Diffuse Large B-Cell Lymphoma
Ongoing Phase 2b SADAL Study in DLBCL. Karyopharm is also investigating oral selinexor as a single-agent for the treatment of patients with relapsed or refractory DLBCL. The SADAL study is expected to enroll up to a total of 130 patients in the single-arm cohort evaluating single-agent selinexor dosed 60mg twice weekly in patients with two or more lines of prior therapy. Karyopharm plans to report top-line results by the end of 2018, and assuming a positive outcome, the Company intends to use the data from the SADAL study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor in this relapsed/refractory DLBCL patient population.
Selinexor in Solid Tumors
Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma Underway. Karyopharm previously reported a successful outcome from the Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. The Phase 3 portion is underway and, assuming a positive outcome on the primary end point of progression free survival, the Company intends to use the data from the Phase 2/3 SEAL study to support a New Drug Application in the U.S. and a Marketing Authorization Application (MAA) in Europe for oral selinexor as a potential new treatment for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated by the end of 2019.
Initiation of Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer Underway. A randomized Phase 2/3 study of selinexor vs. placebo as maintenance therapy in patients with 1-2 prior platinum-based treatments for advanced endometrial cancer lead by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, has been initiated.
Eltanexor
Positive Phase 1/2 Eltanexor Data Presented at ASH (Free ASH Whitepaper) 2017. Data from a Phase 1/2 study evaluating oral eltanexor in 34 patients with heavily pretreated MM was also presented at ASH (Free ASH Whitepaper) 2017. The data showed that eltanexor, both alone or in combination with low-dose dexamethasone, induced responses or disease control and was associated with prolonged survival. The study has been expanded to evaluate eltanexor in patients with advanced colorectal cancer (CRC), castration-resistant prostate cancer (crPC), and myelodysplastic syndrome (MDS). These are indications where selinexor and XPO1 inhibition has shown clear activity, but where the reduced side effects of eltanexor may permit more extended dosing.
Fourth Quarter and Year Ended December 31, 2017 Financial Results
Cash, cash equivalents and investments as of December 31, 2017, including restricted cash, totaled $176.4 million, compared to $175.5 million as of December 31, 2016.
For the year ended December 31, 2017, research and development expense was $107.3 million compared to $86.9 million for the year ended December 31, 2016. For the year ended December 31, 2017, general and administrative expense was $24.9 million compared to $23.9 million for the year ended December 31, 2016.
Karyopharm reported a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017, compared to a net loss of $109.6 million, or $2.92 per share, for the year ended December 31, 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the years ended December 31, 2017 and December 31, 2016, respectively.
For the quarter ended December 31, 2017, research and development expense was $34.8 million compared to $20.7 million for the quarter ended December 31, 2016. The increase in research and development expenses resulted primarily from increased expenses on our late stage clinical trials for selinexor and from payments of a portion of the upfront fees we received under our license agreement with Ono. For the quarter ended December 31, 2017, general and administrative expense was $6.2 million compared to $6.5 million for the quarter ended December 31, 2016. Karyopharm reported a net loss of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017, compared to a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016. Net loss includes stock-based compensation expense of $4.5 million and $5.1 million for the quarters ended December 31, 2017 and December 31, 2016, respectively.
Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations through at least the first quarter of 2019. These plans include the continued clinical development of selinexor in the Company’s lead indications with a focus on filing an NDA with the FDA requesting accelerated approval in MM during 2018, assuming positive data from the STORM study, and preparing the commercial infrastructure for the potential launch of selinexor in the United States. Additional key milestones expected in 2018 include a potential MAA filing to the EMA requesting conditional approval for selinexor in MM, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.
Conference Call Information
Karyopharm will host a conference call today, Thursday, March 15, 2018, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2017 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 1181109. An audio recording of the call will be available under "Events & Presentations" in the "Investor" section of Karyopharm’s website, View Source, approximately two hours after the event..
"2017 was a year of significant achievement for Karyopharm where we reported positive clinical data from our lead selinexor programs, including the Phase 1b/2 STOMP study in multiple myeloma (MM), the Phase 2b SADAL study in diffuse large B-cell lymphoma (DLBCL), and the Phase 2/3 SEAL study in liposarcoma, and the subsequent advancement of each study," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are looking forward to an event-driven 2018 beginning at the end of April with top-line results from the Phase 2b STORM study, followed by top-line data from the Phase 2b SADAL study by the year end. Assuming positive outcomes, we plan to use the data from both of these studies to support requests for accelerated approval from the U.S. Food and Drug Administration (FDA) and conditional approval from the European Medicines Agency (EMA) in these indications. On the corporate front, we continue to build out our commercial team in anticipation of a potential selinexor launch in the U.S. in 2019."
Fourth Quarter 2017 and Recent Events
New Strategic Relationships
Biogen’s Acquisition of KPT-350 for the Treatment of Neurological and Neurodegenerative Diseases. In January 2018, Karyopharm announced its entry into an agreement with Biogen to acquire Karyopharm’s investigational oral SINE compound KPT-350 targeting certain neurological and neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS). The transaction carries a total deal value of up to $217 million, plus royalties.
Exclusive License Agreement with Ono Pharmaceutical Co., Ltd. (Ono) to Develop and Commercialize Selinexor and Eltanexor in Japan and Other Countries in Asia. In October 2017, Karyopharm announced its entry into an exclusive license agreement with Ono for the development and commercialization of selinexor and eltanexor. The agreement includes the development of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in Japan, South Korea, Taiwan, Hong Kong, and the ASEAN countries (the Territory). The transaction carries a total deal value of up to $193.0 million based on the exchange rate on the effective date of the license agreement plus royalties. Karyopharm retains all rights to selinexor and eltanexor outside the Territory.
Selinexor in Multiple Myeloma
Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. Karyopharm expects to report top-line data from the expanded STORM study cohort at the end of April 2018, and, assuming a positive outcome, intends to use the data from this study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor for penta-refractory MM. The Phase 2b STORM study was previously expanded to include 122 additional patients with penta-refractory MM.
Pivotal Phase 3 BOSTON Study Underway. Karyopharm’s pivotal, randomized Phase 3 BOSTON (Bortezomib, Selinexor and dexamethasone) study is now underway and enrolling patients in 14 countries globally. BOSTON is designed to evaluate 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and dexamethasone (SVd), compared to standard twice weekly Velcade and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The primary endpoints of the study are progression free survival and overall response rate. Both the trial design and endpoints have been agreed to by the FDA and the EMA as acceptable to support an application for approval. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and is expecting completion of enrollment in 2018, with top-line data anticipated in 2019.
Positive Phase 1b/2 STOMP Data Presented at ASH (Free ASH Whitepaper) 2017. Data presentations featuring clinical results from four treatment arms of the ongoing Phase 1b/2 STOMP study evaluating selinexor in combination with standard therapies for the treatment of patients with MM were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting (ASH 2017). Collectively, the STOMP study data presented at ASH (Free ASH Whitepaper) 2017 continue to provide evidence of tolerability and robust anti-myeloma activity when selinexor is combined with the currently available standard myeloma therapies, including proteasome inhibitors including Velcade, immunomodulatory drugs and anti-CD38 monoclonal antibodies. Additional treatment arms with selinexor in patients with newly diagnosed disease in combination with lenalidomide, and in combination with the proteasome inhibitor Kyprolis (carfilzomib) have been added.
Selinexor in Diffuse Large B-Cell Lymphoma
Ongoing Phase 2b SADAL Study in DLBCL. Karyopharm is also investigating oral selinexor as a single-agent for the treatment of patients with relapsed or refractory DLBCL. The SADAL study is expected to enroll up to a total of 130 patients in the single-arm cohort evaluating single-agent selinexor dosed 60mg twice weekly in patients with two or more lines of prior therapy. Karyopharm plans to report top-line results by the end of 2018, and assuming a positive outcome, the Company intends to use the data from the SADAL study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor in this relapsed/refractory DLBCL patient population.
Selinexor in Solid Tumors
Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma Underway. Karyopharm previously reported a successful outcome from the Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. The Phase 3 portion is underway and, assuming a positive outcome on the primary end point of progression free survival, the Company intends to use the data from the Phase 2/3 SEAL study to support a New Drug Application in the U.S. and a Marketing Authorization Application (MAA) in Europe for oral selinexor as a potential new treatment for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated by the end of 2019.
Initiation of Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer Underway. A randomized Phase 2/3 study of selinexor vs. placebo as maintenance therapy in patients with 1-2 prior platinum-based treatments for advanced endometrial cancer lead by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, has been initiated.
Eltanexor
Positive Phase 1/2 Eltanexor Data Presented at ASH (Free ASH Whitepaper) 2017. Data from a Phase 1/2 study evaluating oral eltanexor in 34 patients with heavily pretreated MM was also presented at ASH (Free ASH Whitepaper) 2017. The data showed that eltanexor, both alone or in combination with low-dose dexamethasone, induced responses or disease control and was associated with prolonged survival. The study has been expanded to evaluate eltanexor in patients with advanced colorectal cancer (CRC), castration-resistant prostate cancer (crPC), and myelodysplastic syndrome (MDS). These are indications where selinexor and XPO1 inhibition has shown clear activity, but where the reduced side effects of eltanexor may permit more extended dosing.
Fourth Quarter and Year Ended December 31, 2017 Financial Results
Cash, cash equivalents and investments as of December 31, 2017, including restricted cash, totaled $176.4 million, compared to $175.5 million as of December 31, 2016.
For the year ended December 31, 2017, research and development expense was $107.3 million compared to $86.9 million for the year ended December 31, 2016. For the year ended December 31, 2017, general and administrative expense was $24.9 million compared to $23.9 million for the year ended December 31, 2016.
Karyopharm reported a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017, compared to a net loss of $109.6 million, or $2.92 per share, for the year ended December 31, 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the years ended December 31, 2017 and December 31, 2016, respectively.
For the quarter ended December 31, 2017, research and development expense was $34.8 million compared to $20.7 million for the quarter ended December 31, 2016. The increase in research and development expenses resulted primarily from increased expenses on our late stage clinical trials for selinexor and from payments of a portion of the upfront fees we received under our license agreement with Ono. For the quarter ended December 31, 2017, general and administrative expense was $6.2 million compared to $6.5 million for the quarter ended December 31, 2016. Karyopharm reported a net loss of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017, compared to a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016. Net loss includes stock-based compensation expense of $4.5 million and $5.1 million for the quarters ended December 31, 2017 and December 31, 2016, respectively.
Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations through at least the first quarter of 2019. These plans include the continued clinical development of selinexor in the Company’s lead indications with a focus on filing an NDA with the FDA requesting accelerated approval in MM during 2018, assuming positive data from the STORM study, and preparing the commercial infrastructure for the potential launch of selinexor in the United States. Additional key milestones expected in 2018 include a potential MAA filing to the EMA requesting conditional approval for selinexor in MM, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.
Conference Call Information
Karyopharm will host a conference call today, Thursday, March 15, 2018, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2017 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 1181109. An audio recording of the call will be available under "Events & Presentations" in the "Investor" section of Karyopharm’s website, View Source, approximately two hours after the event.