Karyopharm Therapeutics Inc. (KPTI) Q4 2025 Earnings Call Transcript
Access earnings results, analyst expectations, report, slides, earnings call, and transcript.
Overview
The earnings call reflects strong financial guidance, a promising Phase III trial for myelofibrosis, and a strategic focus on growth and financial discipline. Q&A insights highlight positive analyst sentiment and manageable safety profiles. Despite some uncertainties in management responses, the optimistic outlook on selinexor's potential and strategic market positioning suggests a positive stock reaction. The absence of negative catalysts like guidance cuts or financial distress further supports a positive sentiment.
Key Financial Performance
Total revenue for Q4 2025 $34.1 million, an increase of 11.8% compared to Q4 2024. The increase was attributed to higher product sales and licensing revenue.
Total revenue for full year 2025 $146.1 million, a slight increase from 2024. The increase was driven by consistent product demand and licensing revenue.
U.S. XPOVIO net product revenue for Q4 2025 $32.1 million, an increase of 9.6% compared to Q4 2024. The growth was due to consistent demand in the community setting.
U.S. XPOVIO net product revenue for full year 2025 $114.9 million, an increase of 1.9% from 2024. The increase was attributed to steady demand and positioning in the market.
Gross to net provisions for XPOVIO 26.9% in Q4 2025 and 31.2% for the calendar year 2025. No specific reasons for change were mentioned.
License and other revenue for Q4 2025 $2 million. This was part of the total $31.2 million for the full year 2025, which included $15 million of R&D reimbursement from Menarini and $16.2 million from royalties and milestones.
Research and development expenses for Q4 2025 $27.7 million, a decrease of 17% from Q4 2024. The decrease was driven by lower personnel costs and focused clinical trial expenses.
Research and development expenses for full year 2025 $125.6 million, a decrease of 12% from 2024. The reduction was due to cost reduction initiatives and prioritization of capital allocation.
Selling, general and administrative expenses for Q4 2025 $22.8 million, a decrease of 16% compared to Q4 2024. The decrease was due to cost reduction initiatives.
Selling, general and administrative expenses for full year 2025 $105.2 million, a decrease of 9% from 2024. The reduction was attributed to cost-saving measures.
Loss from operations for Q4 2025 Improved by approximately 43% compared to Q4 2024. The improvement was due to disciplined expense management.
Loss from operations for full year 2025 Improved by 24% compared to 2024. The improvement was driven by cost reduction initiatives and focused spending.
Interest expense for Q4 2025 $12.6 million, an increase from Q4 2024. The increase was due to higher outstanding debt and interest rates.
Interest expense for full year 2025 $45.8 million, an increase from 2024. The increase was attributed to refinancing activities and higher interest rates.
Other expense for Q4 2025 $10 million compared to $10.1 million of other income in Q4 2024. The change was driven by noncash fair value remeasurements of derivatives and warrants.
Other income for full year 2025 $0.2 million compared to $28.4 million in 2024. The decrease was due to noncash fair value remeasurements and a loss on extinguishment of debt.
Net loss for Q4 2025 $102.2 million or $5.71 per share. The loss was driven by noncash items like fair value remeasurements and interest expense.
Net loss for full year 2025 $196 million or $17.93 per diluted share. More than half of the loss was due to noncash items, including a loss on extinguishment of debt.
Cash, cash equivalents, restricted cash, and investments as of December 31, 2025 $64.1 million, a decrease from $109.1 million as of December 31, 2024. The decrease was due to operational expenses and debt-related activities.
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Operating Highlights
Selinexor in Myelofibrosis: Phase III SENTRY trial data expected in March 2026. The trial aims to address unmet needs by combining selinexor with ruxolitinib, targeting pathways not addressed by current JAK inhibitors. Early data suggests improved spleen volume reduction, symptom improvement, and lower rates of Grade 3+ anemia.
Selinexor in Endometrial Cancer: Phase III XPORT-EC-042 trial data expected in mid-2026. Focuses on p53 wild-type endometrial cancer with limited treatment options. Early data shows promising progression-free survival (PFS) benefits, with a hazard ratio of 0.36 and median PFS benefit of 39.5 months in specific subgroups.
Myelofibrosis Market Opportunity: Potential to become the first frontline combination therapy with selinexor and ruxolitinib. U.S. market includes 20,000 patients, with 6,000 newly diagnosed annually. Peak revenue opportunity estimated at $1 billion annually in the U.S.
Financial Performance: 2025 total revenue was $146.1 million, with $114.9 million from U.S. XPOVIO net product revenue. Operating expenses decreased due to cost reduction initiatives. Cash runway extends into Q2 2026.
Strategic Focus: Prioritizing late-stage clinical milestones in myelofibrosis and endometrial cancer. Actively evaluating financing and strategic options to align capital decisions with value creation.
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Risk or Challenges
Cash runway and financing: The company’s cash runway extends only into the second quarter of 2026, creating a significant risk of liquidity constraints. The company is actively evaluating financing and strategic options, but this uncertainty could impact operations and strategic flexibility.
Dependence on clinical trial outcomes: The company’s near-term success is heavily dependent on the outcomes of two Phase III trials (SENTRY for myelofibrosis and XPORT-EC-042 for endometrial cancer). Negative or inconclusive results could severely impact the company’s strategic objectives and financial performance.
Competitive pressures in oncology: The company operates in highly competitive markets, including multiple myeloma and myelofibrosis, where established treatments and new entrants could limit market share and revenue growth.
Regulatory and approval risks: The success of the company’s pipeline depends on regulatory approvals for selinexor in new indications. Delays or failures in obtaining these approvals could hinder commercialization efforts.
Supply chain and operational risks: Potential disruptions in the supply chain or operational inefficiencies could impact the production and distribution of selinexor and other products.
Debt and financial obligations: The company faces significant financial obligations, including interest expenses and debt refinancing risks, which could strain financial resources and impact profitability.
Market adoption challenges: Even if approved, selinexor’s adoption in new indications like myelofibrosis may face challenges due to historical concerns about its side effect profile, despite efforts to address these issues with lower dosing and supportive care measures.
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Guidance & Outlook
Myelofibrosis Phase III SENTRY trial: Top-line data expected in March 2026. The trial evaluates selinexor in combination with ruxolitinib, targeting unmet needs in myelofibrosis treatment. The combination aims to improve spleen volume reduction, symptom improvement, and lower rates of Grade 3+ anemia. Potential expansion into other myeloproliferative neoplasms is also being considered.
Endometrial Cancer Phase III XPORT-EC-042 trial: Top-line data expected in mid-2026. The trial focuses on p53 wild-type endometrial cancer patients, aiming to establish selinexor as a maintenance therapy. The trial design includes a lower dose of selinexor and mandated dual antiemetics to improve safety and tolerability.
Revenue Guidance for 2026: Total revenue projected to be $130 million to $150 million, with U.S. XPOVIO net product revenue expected to range from $115 million to $130 million.
Commercial Opportunity in Myelofibrosis: Selinexor combined with ruxolitinib has the potential to become the first frontline combination therapy for myelofibrosis, targeting a $1 billion annual peak revenue opportunity in the U.S. alone. The company is preparing for a rapid launch upon regulatory approval.
Cash Runway: Current liquidity is expected to fund operations into the second quarter of 2026, aligning with key clinical milestones.
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Shareholder Return Plan
The selected topic was not discussed during the call.
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Key Q&A
Q:What are the differences in efficacy and safety between the 40 mg and 60 mg doses in Phase I trials?
A:The 60 mg dose showed a clear benefit-risk profile compared to the 40 mg dose. Efficacy, measured by SVR and TSS, was maximized in the 60 mg group. Safety differences were less stark, with slightly higher heme and non-heme toxicities in the 60 mg group. Pharmacokinetic data also showed higher exposures with the 60 mg dose, supporting its selection for Phase III trials.
Q:What are your thoughts on Novartis' recent plans in the myelofibrosis (MF) space?
A:Novartis' plans highlight the importance of selecting the right patient population and the unmet need in the MF market. Novartis may file in the EU, indicating regulatory flexibility there. However, their U.S. trial will take years to read out, giving Karyopharm time to establish its combination therapy as the standard of care in frontline MF.
Q:What is the strategy for eltanexor and other MPNs if MF data is positive?
A:Eltanexor, a second-generation XPO1 inhibitor, has differentiating properties like lower IC50s and better safety. It has shown encouraging preliminary data in other tumors. The strategy is to expand beyond MF to other MPNs like PV and ET, supported by preclinical data. Eltanexor's patent extends to 2034, with potential extensions to 2039.
Q:Has there been any update on blinded safety data or baseline characteristics in the trial?
A:No updates have been made beyond previously disclosed data. Baseline demographics and TSS evolution align with expectations. Blinded safety data will be definitively analyzed next month, with early indications suggesting manageable toxicities and potentially lower Grade 3+ anemia.
Q:What is the dosing protocol for selinexor and ruxolitinib in the trial?
A:Selinexor doses can be reduced from 60 mg to 40 mg to 20 mg, with re-escalation possible. Ruxolitinib dosing follows local labels, typically based on baseline platelet count. Dose modifications depend on the type of adverse event, with ruxolitinib adjusted for hematologic toxicities and selinexor for non-heme toxicities.
Q:What is the purpose of the SENTRY-2 trial, and how does it fit into the broader strategy?
A:SENTRY-2 aims to explore selinexor as a monotherapy and in combination with other JAK inhibitors. It allows flexibility in treatment and could expand selinexor's role in MF and other MPNs. The trial includes patients with platelets ≥50,000 and offers opportunities for label expansion and guideline inclusion.
Q:How do the Phase III baseline characteristics compare to Phase I/II, and what could this mean for efficacy?
A:Phase III patients appear less sick, with higher baseline hemoglobin and milder disease. However, efficacy is expected to remain consistent across subgroups, as seen in Phase I data. The milder population should not impact the ability to demonstrate meaningful benefit.
Q:What feedback have you received from KOLs and regulators on symptomatic improvement thresholds?
A:KOLs prioritize SVR as the primary treatment driver, with symptoms being secondary. They expect some symptom improvement above ruxolitinib. Regulators have not specified a minimum delta for symptoms, but statistical significance in both SVR and TSS is the goal.
Q:What is the frequency of DSMB safety reviews, and would they detect imbalances in transformations?
A:The DSMB reviews safety data every 4-6 months, including all adverse events, SAEs, and transformations. No issues have been reported so far, and the study continues without modification.
Q:What can you say about dose reductions in the SENTRY trial and their comparison to Phase I?
A:Selinexor dose intensity among the first 61 patients was greater than 95%. Ruxolitinib dose reductions are variable and not meaningful to analyze in the context of blinded data. Further insights will come with top-line data.
Q:Where were the first 61 patients in the SENTRY trial recruited from?
A:The first 61 patients were recruited globally, primarily from North America and Europe, with more patients likely from North America due to earlier site activations.
Q:What gives you confidence in hitting the TSS endpoint in the SENTRY study?
A:Phase I data showed strong TSS50 and absolute TSS improvements. Rapid cytokine reductions correlate with symptom improvement. The FDA allowed a switch to absolute TSS without fatigue, a more sensitive measure. The trial's design and patient population also support confidence in achieving the endpoint.
Q:Review of Unclear Management Responses
A:Management avoided directly addressing the specific dose reductions for ruxolitinib in the SENTRY trial, citing variability in starting doses and the blinded nature of the data. They also did not provide a clear timeline for when in March the Phase III data would be released, only stating it would be 'in March.'
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Earnings Word Cloud
The most frequently occurring keywords in this quarter's earning call
EC trial
Grade anemia
III XPORT
III trial
PFS benefit
PMMR tumor
Phase III
STAT
Slide
XPORT EC
account
antiemetic
beta
capital
checkpoint inhibitor
design Phase
disease
experience
extinguishment debt
franchise
frontline myelofibrosis
income
institution
item
loss share
mid
patient type
program
rate Grade
subgroup
survival
track line
treatment driver
treatment landscape
KPTI Transcript
Karyopharm Therapeutics Inc. (KPTI) Q4 2025 Earnings Call Transcript
Positive2-12
The earnings call reflects strong financial guidance, a promising Phase III trial for myelofibrosis, and a strategic focus on growth and financial discipline. Q&A insights highlight positive analyst sentiment and manageable safety profiles. Despite some uncertainties in management responses, the optimistic outlook on selinexor's potential and strategic market positioning suggests a positive stock reaction. The absence of negative catalysts like guidance cuts or financial distress further supports a positive sentiment.
Karyopharm Therapeutics Inc. (KPTI) Q3 2025 Earnings Call Transcript
Unknown11-3
The earnings call presents a mixed outlook. While financial performance shows improvements in cost management and revenue growth, the company's guidance and liquidity concerns raise uncertainties. The Q&A section highlights potential growth in myelofibrosis treatment but lacks clarity on financing and market positioning. The absence of a strong catalyst like a new partnership or record revenue tempers expectations, resulting in a neutral sentiment.
Karyopharm Therapeutics Inc. (KPTI) Q2 2025 Earnings Call Transcript
Unknown8-11
The earnings call reflects a mixed sentiment. While the company reports decreased R&D and SG&A expenses, an increase in interest expense and a significant net loss raise concerns. The Q&A highlights management's optimism about future trials, yet lacks specifics on enrollment and liquidity strategies. The positive outlook on new data readouts and potential market opportunities is tempered by financial challenges. These mixed signals suggest a neutral impact on stock price, with no strong catalysts for a significant move in either direction.
Karyopharm Therapeutics Inc. (KPTI) Q1 2025 Earnings Call Transcript
Unknown5-13
The earnings call presents a concerning picture with declining revenues, increased product returns, and cash flow risks. Despite passing a futility analysis, clinical trials face enrollment challenges. The lack of a shareholder return plan adds to the negative sentiment. While there is some growth in multiple myeloma, competitive pressures and supply chain issues pose risks. Management's vague responses on cash runway and future risks further contribute to uncertainty. Overall, the sentiment leans negative due to financial instability and competitive market pressures.
KPTI Slides
KPTI Report
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