Here are 1-2 brief analogies for Karyopharm Therapeutics (KPTI):

• Imagine Vertex Pharmaceuticals (known for breakthrough drugs in cystic fibrosis), but instead, Karyopharm focuses on pioneering new targeted therapies for challenging cancers.
• It's like a smaller, more specialized Amgen or Gilead Sciences – major biotechs known for developing innovative drugs – but exclusively dedicated to discovering and developing novel treatments for cancer.

• XPOVIO (selinexor): An oral selective inhibitor of nuclear export (SINE) approved for the treatment of certain relapsed or refractory hematologic malignancies, including multiple myeloma and diffuse large B-cell lymphoma.

Karyopharm Therapeutics (KPTI), as a pharmaceutical company, primarily sells its commercial products to other companies within the healthcare supply chain, rather than directly to individuals. Their major customers are wholesale drug distributors who then supply pharmacies, hospitals, and clinics across the United States. These distributors typically account for a significant majority of Karyopharm's product sales.

The major customer companies for Karyopharm Therapeutics, based on typical pharmaceutical distribution models in the U.S., include:

• McKesson Corporation (Symbol: MCK)
• AmerisourceBergen Corporation (Symbol: ABC)
• Cardinal Health, Inc. (Symbol: CAH)

Lonza (SIX: LONN)

The key risks to Karyopharm Therapeutics (KPTI) are primarily associated with its clinical development pipeline, financial stability, and market competition:

1. Clinical Trial Outcomes and Regulatory Approval: Karyopharm's future success is heavily reliant on the outcomes of its ongoing Phase 3 clinical trials for selinexor in multiple myeloma, endometrial cancer, and myelofibrosis. Failure to achieve positive results in these trials, or delays in securing regulatory approvals, would significantly impact the company's growth prospects and revenue generation.
2. Financial Health and Liquidity: The company has experienced recurring operating losses and possesses a constrained cash runway. Despite recent financing efforts to extend its liquidity, Karyopharm faces substantial debt maturities, including convertible bonds due in October 2025. The need for further external financing or strategic transactions could lead to dilution for existing shareholders or impact the company's valuation. Lower-than-anticipated revenues and high operating expenses continue to pose a challenge to its financial stability.
3. Market Competition and Commercialization Challenges: The therapeutic landscape for multiple myeloma, where Karyopharm's lead product XPOVIO (selinexor) is approved, is intensely competitive with numerous novel treatments entering the market. XPOVIO's sales have historically underperformed initial estimates, suggesting a preference for alternative treatment options and posing risks to future product revenues. Furthermore, the toxicity profile of selinexor is a known limitation that could hinder broader market adoption.

The rapid emergence and increasing adoption of novel immunotherapies, particularly bispecific antibodies, in the treatment of relapsed/refractory multiple myeloma and diffuse large B-cell lymphoma, pose a significant emerging threat to Karyopharm Therapeutics' lead product, XPOVIO (selinexor).

These bispecific antibodies (e.g., teclistamab, elranatamab, talquetamab in multiple myeloma; epcoritamab, glofitamab in DLBCL) offer high response rates and are "off-the-shelf" agents, making them highly competitive in patient populations where XPOVIO is currently utilized. Their continued market penetration and potential shift into earlier lines of therapy could directly impact XPOVIO's market share and growth prospects.

Addressable Markets for Karyopharm Therapeutics' Main Products

Karyopharm Therapeutics (KPTI) has two main commercialized products: XPOVIO (selinexor) and ELZONRIS (tagraxofusp-erzs).

XPOVIO (selinexor)

XPOVIO, also marketed as NEXPOVIO in Europe and the UK, is an oral exportin 1 (XPO1) inhibitor approved for various oncology indications, including multiple myeloma and diffuse large B-cell lymphoma (DLBCL). While specific addressable market sizes for each indication are not explicitly stated, Karyopharm's projected U.S. net product revenue for XPOVIO in 2025 is expected to be in the range of $115 million to $130 million. XPOVIO is also being investigated for use in endometrial cancer. The endometrial cancer market in leading markets (U.S., EU4, UK, and Japan) is expected to grow significantly by 2034, with the United States accounting for the largest market size in 2024, with approximately 68,000 women diagnosed in that year.

ELZONRIS (tagraxofusp-erzs)

ELZONRIS is a treatment for blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare form of leukemia. It is currently the only approved treatment for BPDCN in both the U.S. and Europe. Although specific market size figures for ELZONRIS are not available in the provided information (indicated by redacted values in the source material), North America was identified as the largest region in the ELZONRIS market in 2024. The increasing incidence of leukemia, with cases in the U.S. rising to 62,770 in 2024 from 59,610 in 2023, is contributing to the growth of the ELZONRIS market.

Karyopharm has also identified potential future market opportunities in other rare cancers, representing an estimated $67 million addressable market opportunity, including Waldenstrom Macroglobulinemia with an estimated market size of $42 million annually in the U.S. for approximately 1,500 new cases.

Karyopharm Therapeutics (KPTI) anticipates several key drivers for future revenue growth over the next 2-3 years, primarily centered around its lead compound, selinexor (marketed as XPOVIO).

1. Continued Growth of XPOVIO in Multiple Myeloma (MM): XPOVIO remains the cornerstone of Karyopharm's current revenue, and the company is focused on driving increased sales in the competitive multiple myeloma market. U.S. net product revenue for XPOVIO demonstrated an 8.5% increase in the third quarter of 2025 compared to the same period in 2024. A significant portion of these sales, approximately 60%, continues to be driven by the community setting. Analysts project annual revenue from the MM indication alone to be around $120 million for at least the next decade. The company is also working to expand selinexor's use into earlier lines of therapy for MM.
2. Potential Approval and Commercialization in Myelofibrosis (MF): The pivotal Phase 3 SENTRY trial evaluating selinexor in myelofibrosis is considered the most significant near-term catalyst for Karyopharm. Enrollment for the trial is complete, with top-line data expected in March 2026. Karyopharm projects a peak annual revenue potential of up to approximately $1 billion in the U.S. alone for selinexor in myelofibrosis, anticipating rapid commercial uptake if approved.
3. Potential Approval and Commercialization in Endometrial Cancer (EC): Selinexor is also undergoing evaluation in a Phase 3 trial for advanced/recurrent endometrial cancer. Positive outcomes from this trial could substantially boost revenue. While initial data readouts were anticipated earlier, a more recent update suggests top-line data is now expected in mid-2026, which may affect the timeline for regulatory approvals.
4. Growth in License, Royalty, and Milestone Revenue from International Partners: Karyopharm generates revenue through its international partners, predominantly Menarini and Antengene, who are responsible for the global launches of selinexor. Expanded global patient access to selinexor has led to an increase in royalty revenue, which grew by 28% in the second quarter of 2025 compared to the previous year and increased to $1.5 million in the third quarter of 2025 compared to the third quarter of 2024. The company plans to continue supporting these global launches following regulatory and reimbursement approvals in various ex-U.S. territories.

Share Issuance

• In October 2025, Karyopharm completed a private placement that generated approximately $8.75 million in gross proceeds from the sale of 1.49 million shares and accompanying warrants.
• In October 2025, approximately $24.25 million of senior unsecured convertible notes were exchanged for newly issued common stock or pre-funded warrants, along with additional stock-purchase warrants.
• The company previously completed a private placement yielding approximately $165 million in gross proceeds from the issuance of 31,791,908 shares of common stock and warrants to purchase 9,537,563 shares.

Inbound Investments

• In October 2025, Karyopharm announced comprehensive financing and capital structure transactions providing $100 million of financial flexibility and additional capital.
• This financing included $27.5 million in new term loan borrowings and new convertible notes.
• The transactions also involved a $25 million deferral of interest and royalty payments and a $15 million temporary reduction in the company's minimum liquidity covenant.

Capital Expenditures

• Karyopharm Therapeutics has reported consistently low or negative capital expenditures over the last few years, indicating minimal spending on physical assets.
• Capital expenditures were reported as $0.05 million for the second quarter of 2025 and -$0.14 million for the full fiscal year 2024.
• For fiscal years 2020 through 2023, capital expenditures ranged from approximately -$0.15 million to zero.