On November 8, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the third quarter 2018 and provided an overview of recent accomplishments for selinexor, its lead, novel, oral SINE compound, and its other pipeline programs (Press release, Karyopharm, NOV 8, 2018, View Source [SID1234531001]).

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"We continued to make tremendous progress towards bringing selinexor, our lead drug candidate, to patients with highly refractory multiple myeloma. Most notably, the U.S. FDA has now accepted our New Drug Application (NDA), granting it a Priority Review with an action date of April 6, 2019, under the Prescription Drug User-Fee Act (PDUFA)," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "In this NDA, we are requesting accelerated approval for selinexor as a new treatment for patients with penta-refractory multiple myeloma. If selinexor is approved, we believe that its novel mechanism of action and oral administration, along with its compelling clinical profile, will make it a meaningful treatment option for patients with highly refractory myeloma. Additionally, we continue to believe selinexor holds broad utility beyond highly refractory myeloma. We recently received Fast Track Designation for selinexor in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and were also very pleased to learn that the top-line results from the Phase 2b SADAL study in patients with relapsed or refractory DLBCL have been selected for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 1, 2018. Finally, by the end of 2018, we remain on track to complete enrollment in the pivotal Phase 3 BOSTON study evaluating selinexor in combination with once weekly Velcade and low-dose dexamethasone versus standard twice weekly Velcade – dexamethasone in patients with multiple myeloma who have had one to three prior lines of therapy."

"As we await the upcoming FDA review decision for selinexor, we are building our U.S. commercial capabilities, which will include hiring our U.S. sales force in early 2019. In order to strengthen our financial position, we recently increased our cash position through a private offering of convertible senior notes resulting in net proceeds of approximately $166.9 million which helps extend our estimated cash runway into the second quarter of 2020. Additionally, our future capital needs could potentially be partially offset with cash generated from sales of selinexor following commercialization, which could come as early as the second quarter of 2019, pending FDA approval," concluded Dr. Kauffman.

Third Quarter 2018 and Recent Events

Selinexor in Multiple Myeloma

U.S. FDA Accepts Selinexor NDA and Grants Priority Review. The U.S. FDA accepted for filing with Priority Review Karyopharm’s NDA seeking accelerated approval for selinexor, its first in class, oral SINE compound, as a new treatment for patients with penta-refractory multiple myeloma. The FDA also assigned an action date of April 6, 2019 under the PDUFA. Provided marketing approval is granted by the FDA, Karyopharm plans to commercialize selinexor in the U.S. in the first half of 2019. The Company also plans to submit a Marketing Authorization Application to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval.

Phase 2b STORM Data Selected for Oral Presentation at ASH (Free ASH Whitepaper) 2018. Additional results from Part 2 of the Phase 2b STORM study have been selected for oral presentation at the upcoming ASH (Free ASH Whitepaper) 2018 Annual Meeting in early December. Karyopharm previously reported results from the Phase 2b STORM study evaluating selinexor plus low dose dexamethasone (Sd) in patients with penta-refractory multiple myeloma in September at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting. For the STORM study’s primary objective, the overall response rate (ORR) was 26.2%, which included two stringent complete responses (sCRs), six very good partial responses (VGPRs) and 24 partial responses (PRs) in these patients with penta-refractory myeloma. The two sCRs were negative for minimal residual disease, one at the level of 1×10-6 and one at 1×10-4; this is particularly significant in this penta-refractory population. The ORR for Sd in patients who had previously received Darzalex combination therapy (n=86) was 29.1%. The Disease Control Rate for patients who had achieved stable disease or better was 78.6%. All responses were confirmed by an Independent Review Committee. Median progression-free survival (PFS) was 3.7 months and the median duration of response (DOR) was 4.4 months (range <1 to 9.9 months). Median overall survival (OS) across the study was 8.6 months. Median OS in the approximately 40% of patients with at least a minimal response (MR) on Sd was 15.6 months compared to a median OS of 1.7 months in patients whose disease progressed or was not evaluable (p<0.0001). The short median OS of patients with no response to selinexor is consistent with the lack of available effective therapies for the very heavily pretreated population who entered the study. Across the relevant patient population, side effects of oral selinexor were generally predictable and manageable with dose adjustments and/or supportive care, with safety results that were consistent with those previously reported from Part 1 of this STORM study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies.

Two Phase 1b/2 STOMP Abstracts Selected for Presentation at ASH (Free ASH Whitepaper) 2018. Two abstracts featuring clinical data from two treatment arms of the ongoing Phase 1b/2 STOMP study in patients with relapsed or refractory multiple myeloma have been selected for oral and poster presentations at ASH (Free ASH Whitepaper) 2018. The oral presentation will highlight data from the arm evaluating selinexor in combination with Darzalex (daratumumab) and low-dose dexamethasone (SDd). The poster presentation will provide updated data from the arm evaluating selinexor in combination with Pomalyst (pomalidomide) and low-dose dexamethasone (SPd). In data reported previously from these arms, selinexor has demonstrated evidence of additive or synergistic anti-myeloma activity when combined with these standard approved therapies.

Pivotal Phase 3 BOSTON Study in Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is underway and enrolling patients globally. BOSTON is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and low dose dexamethasone (SVd), compared to standard twice weekly Velcade and low dose dexamethasone (Vd) in patients with multiple myeloma who have had one to three prior lines of therapy. The primary endpoints of the study are PFS and ORR. Data from the BOSTON study, if positive, would be used to support regulatory submissions to the FDA and EMA requesting full approvals for use of selinexor in second line multiple myeloma, following the Company’s requests for accelerated and conditional approvals, respectively, using data from the Phase 2b STORM study. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and expects to complete enrollment by the end of 2018, with top-line data anticipated at the end of 2019.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Received Fast Track Designation from FDA for the Treatment of Patients with Relapsed or Refractory DLBCL. In addition to Orphan Drug Designation, selinexor was recently granted Fast Track designation by the FDA for the treatment of patients with relapsed or refractory DLBCL.

Phase 2b SADAL Data in DLBCL Selected for Presentation at ASH (Free ASH Whitepaper) 2018. An abstract featuring data from the fully enrolled Phase 2b SADAL study has been selected for poster presentation at ASH (Free ASH Whitepaper) 2018. The SADAL study is designed to evaluate single agent oral selinexor 60mg for patients with relapsed or refractory DLBCL who are not eligible for stem cell transplantation. The SADAL study has enrolled approximately 125 patients with DLBCL who received two to five lines of prior therapy at single-agent selinexor dosed 60mg twice weekly in patients. Assuming the results from the SADAL study are positive, Karyopharm plans to submit an NDA to the FDA with a request for accelerated approval, and a Marketing Authorization Application (MAA) to the EMA with a request for conditional approval, for oral selinexor in this relapsed or refractory DLBCL patient population.
Selinexor in Solid Tumors

Ongoing Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma. Karyopharm previously reported results from the successful 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. Enrollment and dosing is currently ongoing in the Phase 3 portion of the SEAL study and, assuming a positive outcome on the primary end point of PFS, the Company intends to use the data from the SEAL study to support an NDA and an MAA submission requesting full approval for oral selinexor 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.

Ongoing Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer. A randomized Phase 2/3 study of selinexor versus placebo as maintenance therapy in patients with one or two prior platinum-based treatments for advanced endometrial cancer, led by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, is currently ongoing. In the U.S., endometrial cancer is the most common gynecological cancer with approximately 58,000 cases expected to be diagnosed and an estimated 10,000 women expected to die from this cancer in 20181, revealing a meaningful patient population in need of novel therapies.
Eltanexor

Phase 1/2 Eltanexor Data in Metastatic Colorectal Cancer (mCRC) Presented at ESMO (Free ESMO Whitepaper) 2018. At the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in October, John Hays. MD, PhD, Ohio State University, Comprehensive Cancer Center, presented preliminary results from the ongoing Phase 1/2 investigator-sponsored study investigating eltanexor in patients with heavily pre-treated (median of 4 prior treatment regimens) metastatic colorectal cancer (mCRC). The presented results showed that 37% of patients experienced disease control at ≥8 weeks on eltanexor and the median preliminary progression free survival (PFS) for all patients in the 30 mg cohort was 3.5 months. Eltanexor was generally well tolerated with manageable adverse events. The highest observed treatment-related grade ≥3 adverse events were hyponatremia (23%), fatigue (20%) and anemia (20%). Karyopharm is encouraged by these preliminary results which demonstrated promising efficacy with a median PFS longer than currently available third line therapies and an acceptable safety and tolerability profile.
Other ASH (Free ASH Whitepaper) 2018 Highlights

Several Investigator-sponsored Trials and Preclinical Abstracts Selected for Presentation at ASH (Free ASH Whitepaper) 2018. Three abstracts featuring clinical data from investigator-sponsored clinical studies evaluating selinexor either as a single-agent or in combination with other anti-cancer agents for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and pediatric leukemia have been selected for oral or poster presentations at ASH (Free ASH Whitepaper) 2018. Three abstracts describing preclinical research exploring the use of selinexor in models of multiple myeloma and AML have also been selected for poster presentations at the meeting. One abstract featuring preclinical research investigating the use of KPT-9274, Karyopharm’s oral dual inhibitor of PAK4 and NAMPT, for the treatment of AML, has also been selected for a poster presentation. A complete list of the ASH (Free ASH Whitepaper) 2018 abstracts can be accessed here.
Corporate Updates

Carsten Thiel, Ph.D. Appointed to the Board. Karyopharm announced the appointment of Carsten Thiel, Ph.D., to its Board of Directors. Dr. Thiel is currently Chief Executive Officer of Abeona Therapeutics Inc., a clinical-stage biopharmaceutical company focused on developing novel cell and gene therapies. Prior to joining Abeona, Dr. Thiel served as the Executive Vice President and Chief Commercial Officer of Alexion Pharmaceuticals, Inc., a leading global biopharmaceutical company focused on serving patients affected by rare diseases.
Third Quarter Ended September 30, 2018 Financial Results

Cash, cash equivalents and investments as of September 30, 2018, including restricted cash, totaled $212.3 million, compared to $176.4 million as of December 31, 2017.

On October 26, 2018, Karyopharm completed a private offering securing a $172.5 million aggregate principal amount of 3.00% convertible senior notes due in 2025, including the full exercise of the initial purchasers’ option to purchase additional notes. After deducting the initial purchasers’ discounts and commissions and other offering expenses the net proceeds are estimated to be $166.9 million.

For the quarter ended September 30, 2018, research and development expense was $36.4 million compared to $25.2 million for the quarter ended September 30, 2017. For the quarter ended September 30, 2018, general and administrative expense was $13.0 million compared to $5.8 million for the quarter ended September 30, 2017.

Karyopharm reported a net loss of $48.1 million, or $0.79 per share, for the quarter ended September 30, 2018, compared to a net loss of $30.6 million, or $0.65 per share, for the quarter ended September 30, 2017. Net loss includes stock-based compensation expense of $4.8 million and $4.9 million for the quarters ended September 30, 2018 and September 30, 2017, respectively.

Financial Outlook

Karyopharm expects its operating cash burn, including research and development and general and administrative expenses, for the year ending December 31, 2018 to be in the range of $175 to $185 million. Following Karyopharm’s private placement of convertible senior notes during October 2018, and based on its current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations into the second quarter of 2020. This estimate does not account for any cash generated from product sales that the Company expects to generate from the commercial launch of selinexor, which could come as early as the second quarter 2019, if selinexor is approved by the FDA’s assigned PDUFA date. Karyopharm’s future capital needs could potentially be partially offset by cash generated from these sales of selinexor.

Karyopharm’s current operating plans include the continued clinical development of selinexor in the Company’s lead indications and on preparing the commercial infrastructure and hiring a sales force for the potential launch of selinexor in the U.S. Additional key activities expected in 2018 include preparing for a potential MAA submission to the EMA requesting conditional approval for selinexor in multiple myeloma, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like overall response rate (ORR). Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma, accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies. FDA’s Fast Track designation is available to therapeutics treating an unmet medical need in a serious condition; the Company has received Fast Track designation from the FDA specifically for the population treated in the STORM trial. In light of this recognition that the STORM patient population represents an unmet medical need and the positive data reported in April and September 2018, the Company believes that the STORM study should support its request to the FDA for accelerated approval.

Conference Call Information

Karyopharm will host a conference call today, Thursday, November 8, 2018, at 8:30 a.m. Eastern Time, to discuss the third quarter 2018 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 7946498. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.