NEWTON - Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the fourth quarter and full year ended December 31, 2023.
In addition, Karyopharm highlighted select corporate milestones and provided an overview of its key clinical development programs.
'We made significant progress in 2023 across our clinical pipeline and continued to build on our foundation in the highly competitive multiple myeloma space. The encouraging clinical results that we presented last year reinforce the potential of our three ongoing pivotal Phase 3 trials in addressing critical unmet needs of cancer patients,' said Richard Paulson, President and Chief Executive Officer of Karyopharm. 'Our drive for innovation and progress will continue into 2024, by focusing our resources to advance our Phase 3 trials. We are enthusiastic about the upcoming top-line read-outs from these trials and what they could mean for patients and selinexor's growth potential.'
Fourth Quarter 2023 and Recent Highlights
Research and Development (R&D) Highlights
Long-term exploratory analysis of the pre-specified subgroup of patients with advanced or recurrent TP53 wild-type endometrial cancer (EC) from the Phase 3 SIENDO trial (NCT03555422) was presented at the International Gynecological Cancer Society Annual Global Meeting in Seoul, South Korea, with updated progression-free survival (PFS). As of the September 1, 2023 data cut-off date, median PFS was 27.4 months in the selinexor treatment arm (n=77) as compared to 5.2 months (n=36) in the placebo arm. Immature overall survival data showed an encouraging signal and corroborated the PFS results.
Oral presentation at the 65th American Society of Hematology 2023 Annual Meeting of the updated results from the Phase 1 trial (XPORT-MF-034) evaluating selinexor in combination with ruxolitinib in patients with treatment-naive myelofibrosis (MF) showed encouraging long-term durability. 79% of intent-to-treat (ITT) patients (11 out of 14) treated with 60mg selinexor achieved 35% reduction in spleen volume (SVR35) at week 24, and continued to remain in radiographic response as of the August 1, 2023 data cut-off date. In addition, 58% of the ITT patients (7 out of 12) who achieved symptom improvement of 50% (TSS50) at week 24 also remained in response as of the data cut-off. In general, early cytokine reduction at week 4 was associated with spleen volume reduction at week 24, was sustained until the end of treatment, and is a potential sign of disease modification.
Clinical trial collaboration agreement executed with Bristol Myers Squibb (BMS) to evaluate selinexor in combination with BMS' proprietary investigational cereblon E3 ligase modulator (CELMoD) agent mezigdomide in patients with relapsed/refractory multiple myeloma (MM) progressing after T-cell immunotherapies, potentially adding to the growing body of evidence that selinexor has the potential to show meaningful benefit in combination with MM therapies with differing mechanisms of action; the study of selinexor/mezigdomide enables further evaluation of selinexor's role in maintaining an optimal T-cell environment.
XPOVIO Commercial Performance
Achieved U.S. net product revenue for the year ended December 31, 2023 of $112 million, compared to $120 million for the year ended December 31, 2022. U.S. net product revenue for the fourth quarter of 2023 was $25 million, compared to $31 million for the fourth quarter of 2022. Although demand for XPOVIO continued its growth in the community setting in 2023, it was adversely impacted in the academic setting due to increased competition in the later-lines.
Continued progress in shifting selinexor use into earlier lines of therapy, with patient mix approaching 70% in the second to fourth lines in 2023 versus 55% in 20221.
XPOVIO net product revenue was adversely impacted year-over-year by increased utilization of the KaryForward Patient Assistance Program (PAP), due to MM foundation closures2, contributing to 10% of total demand in 2023 as compared to 5% in 2022, leading to an estimated impact of $6 million. Additionally, increased competition and higher gross-to-net, driven by increased 340B discounts and Medicaid rebates during the year, adversely impacted XPOVIO net product revenue in 2023.
Intellectual Property
The U.S. Patent and Trademark Office issued patents directed toward the polymorphic form of selinexor present in XPOVIO, pharmaceutical compositions comprising the polymorphic form and methods of treatment using the polymorphic form and the pharmaceutical compositions. The newly issued patents will expire in August 2035.
Anticipated Catalysts and Operational Objectives in 2024 and 2025
Present updated exploratory subgroup analysis results in patients with TP53 wild-type EC from the Phase 3 SIENDO trial in 2024.
Complete enrollment in pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type EC in 2H 2024 and report top-line results in 1H 2025.
Report updated results from the Phase 1 trial of selinexor in combination with ruxolitinib in patients with treatment-naive MF in 2024.
Report preliminary results from the Phase 2 trial evaluating the efficacy and safety of selinexor monotherapy in subjects with JAK inhibitor-naive MF and moderate thrombocytopenia in 2H 2024.
Report top-line results from pivotal Phase 3 trial of selinexor in combination with ruxolitinib in treatment-naive MF in 2H 2025.
Publish and present efficacy and safety data on selinexor 40mg in combination with pomalidomide and dexamethasone from ongoing STOMP/028 Phase 2 trials in patients with MM in 2024.
Report additional data on selinexor's impact on T-cell fitness and potential combinability with multiple agents pre- or post-T-cell therapy in patients with MM in 2024.
Complete enrollment in pivotal Phase 3 trial evaluating an oral combination of 40mg selinexor, pomalidomide and dexamethasone in patients with previously treated MM in 2H 2024 and report top-line results in 1H 2025.
Maintain the Company's commercial foundation in the competitive MM marketplace, driving increased XPOVIO revenues.
Continue global launches and reimbursement approvals for selinexor by partners in ex-U.S. territories.
About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, South Korea, Israel, Singapore, Hong Kong, Mainland China, Australia, Canada, Taiwan and Macau and is marketed in those areas by Karyopharm's global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.
Contact:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea, Israel, Singapore, Hong Kong, Mainland China, Australia, Canada, Taiwan and Macau, and is marketed in those areas by Karyopharm's global partners. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer and myelofibrosis.
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 Karyopharm's guidance on its 2024 total revenue, 2024 U.S. net product revenue and 2024 R&D and SG&A expenses; Karyopharm's expected cash runway; expectations with respect to commercialization efforts; the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma, and other diseases and expectations with respect to the clinical development plans and potential regulatory submissions of selinexor and eltanexor. 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 or that any of Karyopharm's drug candidates, including selinexor and eltanexor, 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 the development or commercialization of 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 adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; 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 trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm's business, results of operations and financial condition and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption 'Risk Factors' in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2023, 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, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
XPOVIO and NEXPOVIO are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners.
KARYOPHARM THERAPEUTICS INC. 
