“Our second quarter progress was followed by a transformational milestone: the
Second Quarter 2019 Highlights and Recent Progress
Selinexor in Multiple Myeloma
- XPOVIO™ (selinexor) Receives Accelerated Approval from the
FDA. On July 3, 2019, the FDAapproved oral XPOVIO, Karyopharm’s first-in-class, nuclear export inhibitor. XPOVIO was approved in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. XPOVIO is the first of a novel drug class designated selective inhibitors of nuclear export (SINE) and is the first ever nuclear export inhibitor approved for human use. The first indication is approved under accelerated approval based on response rate. The ongoing Phase 3 BOSTON study will serve as the confirmatory trial for the accelerated approval of XPOVIO. As with all accelerated approvals, continued approval the treatment of myeloma may be contingent upon verification and description of clinical benefit in a confirmatory trial.
- XPOVIO Commercial Launch Underway in the U.S. On
July 9, 2019, XPOVIO became commercially available to patients in the U.S. The commercial launch of XPOVIO is being supported by approximately 70 Karyopharm sales representatives and nurse liaisons as well as an extensive patient and healthcare provider support program called KaryForwardTM. Karyopharm’s commercial efforts are also being supplemented by patient support initiatives coordinated by our dedicated network of participating specialty pharmacy providers. Early prescribing trends are encouraging with robust demand from both academic and community-based physicians throughout the U.S. with early prescriptions being filled for patients with Medicareand commercial insurance coverage.
European Medicines Agency(EMA) Validates Marketing Authorization Application (MAA). In January 2019, Karyopharm submitted a MAA to the EMA requesting conditional approval for selinexor, in combination with dexamethasone, as a new treatment for patients with heavily pretreated multiple myeloma based on the results of the Phase 2b STORM study. As a customary part of the MAA review process, Karyopharm received the consolidated list of questions from EMA in early May 2019and received additional feedback, including the integrated inspection report, based on routine site audits and other activities. The Company promptly addressed the questions and feedback with EMA and the evaluation process of the MAA is ongoing. The Company expects to receive a decision on the application by the end of 2019 or early 2020.
- Pivotal Phase 3 BOSTON Study in
Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is progressing and patient enrollment is complete. Top-line data are expected by the end of 2019 or early 2020 contingent upon the occurrence of progression-free survival (PFS) events, the primary endpoint of the study. The BOSTONstudy is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade® (bortezomib) (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. Data from the BOSTONstudy, if positive, is expected to be used to support regulatory submissions to the FDAand EMA requesting the use of selinexor in patients with multiple myeloma who have received at least one prior therapy.
- New and Updated Phase 1b/2 STOMP Data Presented at
European Hematology Association(EHA) 2019 Annual Meeting. Three selinexor abstracts highlighting new and updated clinical data from patients receiving a combination of selinexor and standard of care myeloma drugs were presented in June at the EHA 2019 Annual Meeting. Specifically, clinical data from the Kyprolis® (carfilzomib), Darzalex® (daratumumab) and Pomalyst® (pomalidomide) arms of the Phase 1b/2 STOMP study were presented. For the Kyprolis arm, once weekly oral selinexor in combination with low dose dexamethasone demonstrated a 78% overall response rate (ORR) in patients with heavily pre-treated, Kyprolis-naïve multiple myeloma. For the Darzalex arm, once weekly oral selinexor in combination with low dose dexamethasone demonstrated a 73% ORR in patients with heavily pre-treated, Darzalex-naïve multiple myeloma. And finally, for the Pomalyst arm, once weekly oral selinexor in combination with low dose dexamethasone demonstrated a 57% ORR in patients with Revlimid® (lenalidomide)-relapsed or -refractory, Pomalyst-naïve multiple myeloma with PFS of 12.2 months. Across all 3 arms of the STOMP study presented, the most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)
- NDA and MAA Expected to be Submitted between Q4 2019 and Q1 2020. Following the positive results from the Phase 2b SADAL study that were first presented at the
America Society of Hematology2018 Annual Meeting and then updated in June at the 2019 International Conference on Malignant Lymphoma, Karyopharm expects to submit a New Drug Application (NDA) to the FDAand an MAA to the EMA requesting accelerated and conditional approval of selinexor, respectively, as a treatment for patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for stem cell transplantation including CAR-T (chimeric antigen receptor modified T cell) therapy. In addition to Orphan Drug Designation, selinexor was granted Fast Track designation by the FDAin 2018.
Selinexor in Solid Tumors
- Ongoing Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma. Karyopharm previously reported positive results from the Phase 2 portion of the randomized, blinded Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. Enrollment is currently ongoing in the Phase 3 portion of the SEAL study. Assuming a positive outcome on the primary endpoint of PFS, the Company intends to use the data from the SEAL study to support NDA and MAA submissions requesting approval for selinexor for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated in 2020.
- Company-Sponsored Phase 3 SIENDO Study Evaluating Selinexor as Maintenance Therapy in Endometrial Cancer Now Underway. During the first quarter of 2019, an Investigational New Drug Application (IND) was submitted and accepted by the
FDAfor a randomized, blinded Phase 2/3 study evaluating selinexor versus placebo as a maintenance therapy in patients with advanced or recurrent endometrial cancer following one prior platinum-based treatment. There are currently no approved therapies to treat patients with advanced or recurrent endometrial cancer in the maintenance setting. The primary endpoint of the SIENDO study is PFS. This study is being led by Professor Ignace Vergote, MD, PhD, Head of the Department of Obstetrics and Gynaecologyand Gynaecologic Oncology at the Catholic University of Leuven, Belgium. Karyopharm is targeting enrollment completion for SIENDO in 2020.
- Updated Phase 2 KING Data in Glioblastoma Presented at
American Society of Clinical Oncology( ASCO) 2019 Annual Meeting. An abstract highlighting updated efficacy and safety results from the Phase 2 KING study evaluating single-agent selinexor in patients with recurrent glioblastoma was presented in June at the ASCO2019 Annual Meeting. The KING study evaluated three different dosing schedules with selinexor (50mg/m2 twice per week, 60mg twice per week and 80mg once per week) and the reported results followed completion of accrual in the non-surgical cohorts in the study (n=68). Based on the efficacy and tolerability results from the study, the 80mg once per week dosing regimen is recommended for further evaluation. Of the 30 patients treated in the 80mg dosing cohort, the overall response rate reported was 10%, with 19% of patients achieving a 6-month PFS rate and 30% of patients achieving a 6-cycle PFS rate. The most common non-hematologic AEs in this cohort were nausea, fatigue, anorexia, and vomiting, all of which were Grade 1 or 2 events. The most common treatment-related hematological AEs were primarily Grade 1 and 2 and included leukopenia, neutropenia, anemia, and thrombocytopenia. There was one case (3%) of Grade 4 treatment-related lymphopenia and no Grade 5 treatment-related AEs were reported.
Founder Sharon Shacham Receives New York Intellectual Property Law Association(NYIPLA) Inventor of the Year Award. In May, Karyopharm’s founder, President and Chief Scientific Officer, Sharon Shacham, PhD, MBA, received the esteemed NYIPLA 2019 “Inventor of the Year” award. Dr. Shacham was recognized for her scientific research that led to the development of oral selinexor and related compounds. Past winners of this award have included the inventors of CAR-T therapy, Gleevec®, Valium®, LASIK laser vision correction and Priceline.com, among many others.
Second Quarter 2019 Financial Results
Cash, cash equivalents and investments as of
License and other revenue for the quarter ended
For the quarter ended
Karyopharm reported a net loss of
2019 Financial Outlook
Based on its current operating plans, Karyopharm expects its non-GAAP operating expenses, which excludes stock-based compensation expense, for the full year 2019 to be in the range of
Non-GAAP Financial Information and Other Disclosures
Karyopharm uses a non-GAAP financial measure, non-GAAP operating expense, to provide operating expense guidance. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP total operating expense and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP operating expense should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP. Karyopharm has not provided GAAP reconciliation for its forward-looking non-GAAP annual operating expense because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the forward-looking non-GAAP financial measure.
Conference Call Information
Karyopharm will host a conference call today,
Important Safety Information
The most common adverse reactions observed in patients treated with XPOVIO (incidence ≥20%) are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.
The treatment discontinuation rate due to adverse reactions was 27%; 53% of patients had a reduction in the XPOVIO dose, and 65.3% had the dose of XPOVIO interrupted. The most frequent adverse reactions requiring permanent discontinuation in 4% or greater of patients who received XPOVIO included fatigue, nausea, and thrombocytopenia. The rate of fatal adverse reactions was 8.9%.
The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.
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 Karyopharm’s expectations relating to XPOVIO for the treatment of patients with heavily pretreated multiple myeloma, commercialization of XPOVIO or any of its drug candidates, submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the anticipated timing of such submissions and actions and the potential availability of accelerated approval pathways, and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or accelerated or conditional approval in the U.S. or EU, respectively, based on the SADAL study in patients with relapsed or refractory DLBCL, or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary 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: the timing and costs involved in commercializing XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; 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
Velcade® is a registered trademark of
Revlimid® and Pomalyst® are registered trademarks of
Kyprolis® is a registered trademark of
Darzalex® is a registered trademark of
Gleevec® is a registered trademark of
Valium® is a registered trademark of
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|Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share amounts)
|Cash and cash equivalents||$||75,545||$||118,021|
|Prepaid expenses and other current assets||5,671||6,413|
|Total current assets||222,830||334,612|
|Property and equipment, net||3,375||3,863|
|Operating lease right-of-use assets||11,180||—|
|Liabilities and stockholders’ equity|
|Operating lease liabilities||1,522||—|
|Other current liabilities||453||327|
|Total current liabilities||32,174||46,904|
|Convertible senior notes||106,157||102,664|
|Operating lease liabilities, net of current portion||14,055||—|
|Deferred revenue, net of current portion||3,245||4,532|
|Deferred rent, net of current portion||—||3,922|
|Preferred stock, $0.0001 par value; 5,000,000 shares authorized; none issued and outstanding||—||—|
|Common stock, $0.0001 par value; 200,000,000 shares authorized; 60,965,505 shares issued and outstanding at June 30, 2019; 100,000,000 shares authorized; 60,829,308 shares issued and outstanding at December 31, 2018||6||6|
|Additional paid-in capital||865,726||857,156|
|Accumulated other comprehensive income (loss)||61||(244||)|
|Total stockholders’ equity||82,469||183,170|
|Total liabilities and stockholders’ equity||$||238,100||$||341,192|
|Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share amounts)
|Three Months Ended,
|Six Months Ended
|License and other revenue||$||9,493||$||19,891||$||9,648||$||29,891|
|Research and development||26,517||44,734||64,491||86,055|
|General and administrative||24,662||9,489||51,765||17,110|
|Total operating expenses||51,179||54,223||116,256||103,165|
|Loss from operations||(41,686||)||(34,332||)||(106,608||)||(73,274||)|
|Other income (expense):|
|Other (expense) income||(44||)||7||(46||)||(7||)|
|Total other (expense) income, net||(1,721||)||660||(2,950||)||1,155|
|Loss before income taxes||(43,407||)||(33,672||)||(109,558||)||(72,119||)|
|Income tax (provision) benefit||(8||)||17||(18||)||5|
|Net loss per share—basic and diluted||$||(0.71||)||$||(0.60||)||$||(1.80||)||$||(1.36||)|
|Weighted-average number of common shares outstanding used in net loss per share—basic and diluted||60,929,024||56,089,159||60,892,860||52,862,194|
Source: Karyopharm Therapeutics Inc.