“It’s been an active first quarter of 2019, which included a
First Quarter 2019 and Recent Events
Selinexor in Multiple Myeloma
- FDA Extends Review Period for NDA to
July 6, 2019. On Feb 26, 2019, the FDAheld an ODAC meeting to review the selinexor NDA requesting accelerated approval. The committee was specifically asked to vote on whether the approval of selinexor should be delayed until the results from the ongoing, randomized Phase 3 BOSTON study are available. In a vote of 8 Yes and 5 No, the ODAC recommended that the approval decision for selinexor should be delayed until the results of the BOSTONstudy are available. Following the ODAC meeting, and at the FDA'srequest, Karyopharm submitted additional, existing clinical information as an amendment to the NDA. On March 14, 2019, the FDAextended the PDUFA action date for the selinexor NDA by three months to July 6, 2019. The NDA is currently under Priority Review by the FDAand is seeking accelerated approval for selinexor in combination with dexamethasone as a new treatment for patients based on the results of the Phase 2b STORM study in patients with triple class refractory multiple myeloma who were previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Although the FDAwill consider the recommendation of the ODAC panel, the final decision regarding the approval of the product is made by the FDAsolely, and the recommendations by the panel are non-binding.
European Medicines Agency(EMA) Validates Marketing Authorization Application (MAA). On January 8, 2019, Karyopharm submitted a MAA to the EMA requesting conditional approval for selinexor, in combination with dexamethasone, as a new treatment for patients based on the results of the Phase 2b STORM study in patients with triple class refractory multiple myeloma who were previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. As a customary part of the marketing application review process, Karyopharm received the consolidated list of questions from EMA in early May 2019and anticipates receiving additional feedback based on routine site audits and other activities. Karyopharm plans to promptly address the questions and feedback with EMA. To provide adequate time to evaluate the application and allow Karyopharm to respond to questions and feedback, the EMA has switched from an accelerated review to a traditional review. The Company expects to receive a decision on the application by the end of 2019.
- Pivotal Phase 3 BOSTON Study in
Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is progressing and, in January 2019, the Company announced the completion of patient enrollment in the study. Top-line data is expected by the end of 2019 or into 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, would be used to support regulatory submissions to the FDAand EMA requesting the use of selinexor in patients with multiple myeloma who received at least one prior therapy. Regulatory approvals based on the results from the BOSTONstudy would also confirm accelerated and/or conditional approvals based on data from the Phase 2b STORM study.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)
- NDA and MAA Expected to be Submitted in the First Half of 2020. Following the positive top-line results from the Phase 2b SADAL study which were presented at ASH 2018, Karyopharm expects to submit an NDA to the
FDAand MAA to the EMA requesting accelerated and conditional approval, respectively, 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) therapies. In addition to Orphan Drug Designation, selinexor was granted Fast Track designation by the FDAin 2018.
Selinexor in Solid Tumors
- Phase 3 SIENDO Study Evaluating Selinexor as Maintenance Therapy in Endometrial Cancer Will Now Be Conducted as a Company Sponsored Study. During the first quarter of 2019, an Investigational New Drug Application (IND) was submitted and accepted by
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 was previously an investigator sponsored study and has subsequently transitioned to a company sponsored study 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.
- 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 and, 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.
- Phase 1/2 Eltanexor Data in Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Presented at ASCO-GU 2019. At the
American Society of Clinical Oncology( ASCO) 2019 Genitourinary Cancers Symposium in February, Jingsong Zhang, MD, PhD, H. Lee Moffitt Cancer Centerand Research Institute, presented preliminary results from an ongoing Phase 1/2 investigator-sponsored study investigating eltanexor (+/- abiraterone) in patients with advanced cancers. The presented results showed that amongst the 23 patients with mCRPC evaluable for efficacy, 9% achieved a partial response and 74% achieved stable disease (≥8 weeks). The median treatment duration was 145 days, with three patients remaining on treatment as of November 19, 2018. Amongst the 30 patients evaluable for safety, treatment-related adverse events (TRAEs) occurring in ≥30% of patients included fatigue (80%; 17% Grade (Gr)≥3), nausea (70%; 0% Gr≥3), decreased appetite (60%; 0% Gr≥3), diarrhea (47%; 3% Gr≥3), weight decreased (47%; 3% Gr≥3), vomiting (40%; 7% Gr≥3), anemia (40%; 13% Gr≥3), neutropenia (33%; 13% Gr≥3), dysgeusia (33%; 0% Gr≥3) and thrombocytopenia (30%; 7% Gr≥3). There were two Gr4 TRAEs (neutropenia and elevated AST). Enrollment in the mCRPC arm of the study is now complete.
$1.25 MillionGrant from the U.S. Department of Defense (DoD) Awardedto Explore Use of Verdinexor in Spinal Cord Injury (SCI). A $1.25 milliongrant from the DoD was secured by an academic collaborator, with the assistance of Karyopharm, to study verdinexor (KPT-335) in preclinical models of SCI. The goal of this research is to establish the extent to which oral administration of verdinexor promotes tissue preservation and recovery of function following spinal cord injury. Verdinexor is also being studied as a potential anti-viral agent in a variety of human viral indications and for the treatment of systemic lupus erythematosus (SLE). For SLE, a $2.0 milliongrant was awarded from the National Institute of Healthin 2018 and research is ongoing. The purpose of this grant is to investigate oral verdinexor activity in models of B-cell generation, double-stranded DNA antibody levels, and persistence of self-reactive antibody secreting cells.
Medical Congress Activity and Presentation of Data
- Two Selinexor Abstracts Selected for Presentation at
ASCO2019. Two selinexor abstracts have been selected for presentations at the upcoming ASCO2019 Annual Meeting taking place May 31-June 4, 2019in Chicago. The first abstract, titled “Efficacy and Safety of Selinexor in Recurrent Glioblastoma,” (Lassman, et al; Abstract #2005) was selected for an oral presentation and describes results from the Phase 2 KING study evaluating single-agent selinexor in patients with recurrent glioblastoma. The second abstract, titled “Overall Survival (OS) with Oral Selinexor Plus Low Dose Dexamethasone (Sd) in Patients with Triple Class Refractory-Multiple Myeloma (TCR-MM),” (Richardson, et al; Abstract #8014; Poster Board #340) was selected for a poster presentation and highlights overall survival (OS) data from the Phase 2b STORM study evaluating selinexor and low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available.
- Seven Preclinical Abstracts Presented at AACR 2019. Seven posters highlighting preclinical data for selinexor were presented at the recent
American Association for Cancer Research(AACR) 2019 Annual Meeting. These posters described research evaluating selinexor in various preclinical models of high unmet need cancers, including multiple myeloma, chronic lymphocytic leukemia, breast, pancreatic, lung and metastatic brain cancers. A complete list of these presentations can be accessed by visiting the AACR 2019 website at https://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=174.
- Michael P. Mason Appointed Chief Financial Officer. Karyopharm appointed
Michael P. Masonas Chief Financial Officer. Mr. Mason formerly served as Vice President of Finance and Treasurer at Alnylam Pharmaceuticals, Inc., a public biopharmaceutical company. He brings over 18 years of diversified financial experience to Karyopharm and has extensive expertise in global financial operations and controls, financing transactions, business planning and supporting pharmaceutical product launches.
Tina Clark Beamon, Esq., Appointed Chief Compliance Officer. Karyopharm appointed Tina Clark Beamon, Esq.as Chief Compliance Officer. Ms. Beamon formerly served as Executive Director of Compliance and Ethics at Alexion Pharmaceuticals. Prior to Alexion, she served as the head attorney for the Oncology Division and the Consumer Healthcare Division at Boehringer Ingelheim USA Corporation. She brings 21 years of healthcare industry experience to Karyopharm and will serve an integral role in building upon Karyopharm’s existing high operating standards and its ongoing commitment to corporate compliance and ethics.
First 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
Based on its current operating plans, which assume a selinexor commercial launch by
Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma
Conference Call Information
Karyopharm will host a conference call today,
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 our expectations relating to 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, the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor, the plans for commercialization and financial outlook and projections. 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 regulators will agree that selinexor qualifies for accelerated approval in the U.S. or conditional approval in the E.U. as a result of our clinical data, including the data from the STORM study in patients with triple class refractory myeloma or 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: 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
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Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share amounts)
|Cash and cash equivalents||$||83,506||$||118,021|
|Prepaid expenses and other current assets||7,011||6,413|
|Total current assets||271,435||334,612|
|Property and equipment, net||3,617||3,863|
|Operating lease right-of-use assets||11,448||—|
|Liabilities and stockholders’ equity|
|Operating lease liabilities||1,375||—|
|Other current liabilities||701||327|
|Total current liabilities||43,860||46,904|
|Convertible senior notes||104,368||102,664|
|Operating lease liabilities, net of current portion||14,457||—|
|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, $0.0001 par value; 100,000,000 shares authorized; 60,864,445 and 60,829,308 shares issued and outstanding at March 31, 2019 and December 31, 2018, respectively||6||6|
|Additional paid-in capital||861,215||857,156|
|Accumulated other comprehensive loss||(28||)||(244||)|
|Total stockholders’ equity||121,284||183,170|
|Total liabilities and stockholders’ equity||$||287,214||$||341,192|
Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share amounts)
|Three Months Ended
|License and other revenue||$||155||$||10,000|
|Research and development||37,974||41,321|
|General and administrative||27,103||7,621|
|Total operating expenses||65,077||48,942|
|Loss from operations||(64,922||)||(38,942||)|
|Other income (expense):|
|Total other income (expense), net||(1,229||)||495|
|Loss before income taxes||(66,151||)||(38,447||)|
|Income tax provision||(10||)||(12||)|
|Net loss per share—basic and diluted||$||(1.09||)||$||(0.78||)|
|Weighted-average number of common shares outstanding used in net loss per share—basic and diluted||60,856,295||49,602,809|
Source: Karyopharm Therapeutics Inc.