Karyopharm Reports Third Quarter 2024 Financial Results and Highlights Recent Company Progress

– Achieves Third Quarter 2024 Total Revenue of $38.8 Million and U.S. XPOVIO® (selinexor) Net Product Revenue of $29.5 Million; Continued Regulatory and Reimbursement Approvals Globally,

– Following FDA Alignment, Absolute Change in Total Symptom Score (Abs-TSS) Will Replace TSS50 as a Co-Primary Endpoint in Phase 3 SENTRY Trial in JAKi Naïve Myelofibrosis (MF); Expected Top-line Data Read-out Remains on Track for 2H 2025,

– Narrows Full-Year 2024 Total Revenue Guidance Range to $145.0 Million to $155.0 Million; U.S. XPOVIO Net Product Revenue Guidance Range to $110.0 Million to $115.0 Million; R&D and SG&A Expense Guidance Range to $255.0 Million to $265.0 Million,

NEWTON, Mass., Nov. 5, 2024 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the quarter ended September 30, 2024, and highlighted select corporate milestones and progress on its key clinical development programs.

"This quarter, we delivered our third consecutive quarter of U.S. XPOVIO net product revenue growth in the highly competitive multiple myeloma marketplace. On our clinical pipeline, we are very excited with the change to our Phase 3 SENTRY myelofibrosis trial endpoints following engagement with the FDA, strengthening our confidence for a successful outcome for this trial. We continue to drive disciplined expense management and trial execution as we look forward to our next phase of growth with potential new indications in myelofibrosis and endometrial cancer," said Richard Paulson, President and Chief Executive Officer of Karyopharm.

"A significant unmet need in myelofibrosis remains, as less than half of patients achieve SVR35 with each of the approved JAKi inhibitors. I am encouraged by the Phase 1 trial which evaluated the combination of selinexor and ruxolitinib, as it shows an approximate doubling of SVR35 to 80% compared to historical JAKi monotherapy and a meaningful 18.5 point improvement in Abs-TSS at week 24 compared to baseline," said Dr. John Mascarenhas, Principal Investigator of the Phase 3 SENTRY trial, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "The change to Abs-TSS as a co-primary endpoint signifies a new era in the evaluation of combination therapy and reflects a growing willingness by the FDA to incorporate more sensitive methods of evaluating symptoms in trials with active comparators."

Third Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue of $29.5 million for the third quarter of 2024, compared to $28.0 million for the second quarter of 2024 and $30.2 million for the third quarter of 2023.

XPOVIO net product revenue was supported by quarter-over-quarter double digit growth in demand, partially offset by higher gross-to-net quarter-over-quarter largely due to higher proportion of 340B book of business.

Continued quarter-over-quarter demand growth with strong demand growth in the community setting, which represents approximately 60% of overall net product revenues. In the academic setting, demand for XPOVIO grew quarter-over-quarter amidst ongoing competitive pressures with continued use of XPOVIO preceding and following T-cell therapies in later lines.

Expanded global patient access for selinexor in the third quarter of 2024 with favorable reimbursement decisions in France and Italy and additional regulatory approvals in Turkiye, South Korea, Thailand and Malaysia.

Research and Development (R&D) Highlights

Myelofibrosis

Following recent alignment with the FDA, absolute change in total symptom score (Abs-TSS) at Week 24 will replace total symptom improvement of ≥ 50% (TSS50) as a co-primary endpoint in the pivotal Phase 3 SENTRY trial of selinexor in combination with ruxolitinib in JAKi naive myelofibrosis. Abs-TSS measures the average improvement in patient symptom scores over 24 weeks relative to the patient's baseline symptom score and is an accepted measure that has been used in other Phase 3 clinical trials in myelofibrosis to evaluate the benefit/risk of an add-on treatment, such as selinexor, to the current standard of care. Spleen volume reduction ≥35% (SVR35) at Week 24 will remain as a co-primary endpoint. These two co-primary endpoints will be tested sequentially starting with SVR35 followed by Abs-TSS.

Proactively increasing the total sample size of the SENTRY trial to approximately 350 patients to further increase the statistical powering. The trial continues to enroll patients with strong momentum with expected top-line data read-out remaining in the second half of 2025.

SENTRY-2 Phase 2 trial of selinexor monotherapy in JAKi naïve patients with moderate thrombocytopenia continues to enroll patients. The Company expects to present preliminary data from this trial in late 2024 or early 2025.

Endometrial Cancer

Long-term follow-up data from a pre-specified exploratory subgroup analysis of patients with advanced or recurrent TP53 wild-type endometrial cancer from the SIENDO study (NCT03555422) were presented with expanded exploratory quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) for the proficient mismatched repair status (pMMR) TP53 wild-type subgroup at the International Gynecological Cancer Society (IGCS) conference in October 2024. These data showed the restricted mean Q-TWiST for selinexor to be 30 months compared to 17 months for placebo, resulting in a difference of 13 months.

Pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer continues to enroll patients and is expected to read-out top-line data in early 2026.

Multiple Myeloma

Pivotal XPORT-MM-031 (EMN29) Phase 3 trial, in collaboration with the European Myeloma Network, evaluating an oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd) in patients with previously treated multiple myeloma now has a targeted enrollment of approximately 120 patients which leverages the positively evolving data observed with SPd 40 mg. Pending regulatory agency feedback on the updated protocol, the Company will provide guidance on the top-line data readout timeline from this trial.

2024 Financial Outlook

Based on its current operating plans, Karyopharm has further narrowed its guidance for full year 2024 as follows:

Total revenue to be in the range of $145.0 million to $155.0 million as compared to the Company's prior guidance of $145.0 million to $160.0 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.

U.S. XPOVIO net product revenue to be in the range of $110.0 million to $115.0 million as compared to the Company's prior guidance of $105.0 million to $120.0 million.

R&D and selling, general and administrative (SG&A) expenses to be in the range of $255.0 million to $265.0 million, which includes approximately $20.0 million estimated non-cash stock-based compensation expense, as compared to the Company's prior guidance of $250.0 million to $265.0 million.

The Company expects that its existing cash, cash equivalents and investments, the revenue it expects to generate from XPOVIO net product sales and its license agreements and ongoing disciplined expense management and cost saving measures, will be sufficient to fund its planned operations into the first quarter of 2026.1 

1Excluding re-payment of $24.5 million aggregate principal amount of the Company's remaining senior convertible notes due October 2025 (the 2025 Notes) and $25.0 million minimum liquidity covenant under the Company's senior secured term loan due 2028. Taking into account the repayment of the 2025 Notes and the minimum liquidity covenant, Karyopharm expects its cash, cash equivalents and investments will be sufficient to fund its operations into the fourth quarter of 2025.

Third Quarter 2024 Financial Results

Total revenue: Total revenue for the third quarter of 2024 was $38.8 million, compared to $36.0 million for the third quarter of 2023.

Net product revenue: Net product revenue for the third quarter of 2024 was $29.5 million, compared to $30.2 million for the third quarter of 2023.

License and other revenue: License and other revenue for the third quarter of 2024 was $9.3 million, compared to $5.8 million for the third quarter of 2023. The increase was primarily due to $6.0 million of milestone-related revenue recognized from Menarini, which was related to reimbursement approvals for NEXPOVIO in the third quarter of 2024, partially offset by a $3.3 million decrease in revenue related to the reimbursement of development-related expenses from Menarini due to timing of reimbursement.

Cost of sales: Cost of sales for the third quarter of 2024 was $1.3 million, compared to $0.9 million for the third quarter of 2023. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the third quarter of 2024 were $36.1 million, compared to $35.6 million for the third quarter of 2023. The increase was primarily due to an increase in clinical trial and related costs, mainly driven by increased activity in the ongoing Phase 3 SENTRY trial in myelofibrosis.

SG&A expenses: SG&A expenses for the third quarter of 2024 were $27.6 million, compared to $30.8 million for the third quarter of 2023. The decrease was primarily due to our ongoing cost reduction initiatives and lower headcount.

Interest income: Interest income for the third quarter of 2024 was $1.8 million, compared to $2.8 million for the third quarter of 2023 due to a lower cash and investments balance quarter-over-quarter.

Interest expense: Interest expense for the third quarter of 2024 was $11.4 million, compared to $6.1 million for the third quarter of 2023. The increase in interest expense was due to the Company's new term loan and new secured convertible senior notes.

Other income: Other income for the third quarter of 2024 was $3.8 million due to a non-cash gain recognized in connection with the remeasurement of embedded derivatives and liability classified common stock warrants. The Company had immaterial other income in the third quarter of 2023.

Net loss: Karyopharm reported a net loss of $32.1 million, or $0.26 loss per basic and diluted share, for the third quarter of 2024, compared to a net loss of $34.5 million, or $0.30 loss per basic and diluted share, for the third quarter of 2023.

Cash position: Cash, cash equivalents, restricted cash and investments as of September 30, 2024 totaled $133.9 million, compared to $192.4 million as of December 31, 2023.

Conference Call Information

Karyopharm will host a conference call today, November 5, 2024, at 8:00 a.m. Eastern Time, to discuss the third quarter 2024 financial results and provide business highlights. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company's website. An archived webcast will be available on the Company's website approximately two hours after the event.

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 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) under accelerated approval 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, China, South Korea and Israel, 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.

For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email:

XPOVIO® (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

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, ...