Karyopharm's Q3 2025 Earnings Call: Contradictions in Sales Force Expansion, TSS Impact, Myelofibrosis Enrollment, and Selinexor Dosing

Date of Call: November 3, 2025

Financials Results

• Revenue: $44.0M total revenue in Q3 2025, up 13.4% YOY vs $38.8M in Q3 2024; U.S. XPOVIO net product revenue $32.0M, up 8.5% YOY vs $29.5M
• EPS: $-3.82 per share (GAAP net loss); prior-period EPS not provided

Guidance:

• Total 2025 revenue expected $140M–$155M (includes U.S. XPOVIO and partner license/royalty/milestone revenue)
• U.S. XPOVIO net product revenue expected $110M–$120M
• R&D and SG&A expenses guidance lowered to $235M–$245M
• Gross-to-net provisions expected to remain ~27% in Q4 (consistent with Q3)
• Existing liquidity and recent financing expected to fund operations into Q2 2026; Q4 license revenue primarily royalties

Business Commentary:

* Clinical Progress and Financial Flexibility: - Karyopharm Therapeutics completed enrollment in the Phase III SENTRY trial for frontline myelofibrosis, marking a pivotal moment. - The company secured approximately $100 million in financial flexibility through refinancing, extending its cash runway into Q2 2026. - These milestones were driven by significant clinical progress and a strategic focus on strengthening financial flexibility.

• Revenue and Product Growth:
• Karyopharm reported total revenue of $44 million in Q3, an 13% increase year-over-year, with U.S. net product revenue growing 8.5% to $32 million.

• Growth was attributed to the continued strength of XPOVIO in multiple myeloma and disciplined execution across commercial and operational teams.

• Phase III SENTRY Trial and Top-line Data Expectations:

• The top-line results from the Phase III SENTRY trial are expected in March 2026, with primary endpoints being SVR35 and absolute TSS.
• The trial's success is optimized by aligning co-primary endpoints with FDA guidance and having a higher baseline TSS of approximately 22.5.

• This design is expected to provide meaningful improvement over ruxolitinib alone and validate the relevance of XPO1 inhibition in hematological malignancies.

• Market Potential and Commercial Strategy:

• Karyopharm's potential market opportunity in myelofibrosis is estimated at up to approximately $1 billion annually in the U.S., driven by more than 4,000 annual frontline patient cases.
• The company plans to launch a new frontline combination therapy, working closely with physicians and payers, with high intent to prescribe the combination therapy among physicians.

Sentiment Analysis:

Overall Tone: Positive

• Management highlighted completion of Phase III SENTRY enrollment and top-line readout expected March 2026; secured ~ $100M of financing and extended cash runway into Q2 2026; reported Q3 revenue of $44M (+13% YOY) and noted a ~42% improvement in loss from operations versus prior year — framing the call around clinical progress and improved financial flexibility.

Q&A:

• Question from Peter Lawson (Barclays): Can you walk through what we should see in the MF data in March '26 (SVR, TSS, OS trends, staging of data across 2026) and then how many sales reps you would add/dedicate to MF and your ex-U.S. strategy?
  Response: Top-line SENTRY readout expected March 2026 reporting co‑primary endpoints (SVR35 at week 24 and absolute TSS) plus safety and select secondaries; minimal incremental U.S. commercial hires expected due to ~80% account overlap and existing academic coverage; ex‑U.S. launches will be executed through existing partners.

• Question from Edward Tenthoff (Piper Sandler): Are there any milestones, warrants or financing triggers tied to data that could extend capital beyond the current runway, and are there any geographies without distributors for myelofibrosis?
  Response: There are no financing warrants or specific triggers tied to positive MF data; global partner coverage is in place for selinexor except Japan remains unpartnered.

• Question from Colleen Hanley (Robert W. Baird): Given the baseline TSS (~22.5) versus Phase I, how should we think about read‑through from Phase I to Phase III? And do baseline platelet counts (above/below 200k) affect activity?
  Response: Baseline TSS ~22.5 is encouraging and supports potential for meaningful absolute TSS improvement versus historical ruxolitinib data (Phase I small sample caveat); >50% of patients have platelets >200k and platelet count is not expected to materially impact SVR35 or absolute TSS.

• Question from Maurice Raycroft (Jefferies): What will be included in the ASH abstract and any additional conference data, and are the lower TEAE‑leading‑to‑discontinuation rates seen in the 61‑patient blinded safety snapshot reflective of the full study?
  Response: ASH is an abstract‑only release showing baseline characteristics (~320 patients); full ITT/top‑line data will be presented in March 2026; the 61‑patient blinded safety snapshot shows stable, non‑accumulating discontinuation rates over follow‑up and is therefore encouraging but preliminary.

• Question from Brian Abrahams (RBC Capital Markets): On the 75% physician intent to treat with the combo, which patients would physicians use it in, any payer feedback, and how might emerging targeted agents affect positioning?
  Response: Market research indicates physicians would use the combo in newly diagnosed intermediate‑to‑high‑risk patients with platelets >100k (add selinexor to planned ruxolitinib, not replace it); company does not anticipate payer pushback and views strong physician appetite despite future targeted agents.

• Question from Jonathan Chang (Leerink): What learnings from the multiple myeloma commercial and clinical experience are being applied to a potential myelofibrosis launch?
  Response: MM learnings applied include lower selinexor dosing (60 mg once weekly) and proactive dual antiemetic use to improve tolerability; MF market is less crowded than MM and strong commercial overlap supports a rapid launch if approved.

Contradiction Point 1

Sales Force Expansion and Ex-U.S. Strategy

It involves the company's plans for expanding its sales force and its ex-U.S. strategy for myelofibrosis, which are crucial for market penetration and revenue growth.

What details will be provided on myelofibrosis data (including SVR, TSS, OS trends) and when will the data be presented at medical meetings in 2026? How many sales reps will be added for MF and what is the international strategy? - Peter Lawson (Barclays Bank PLC, Research Division)

2025Q3: Minimal additions to the commercial structure due to strong overlap. Ex-U.S. strategy involves working with existing partners for launches and royalty milestones. - Sohanya Cheng(CMO)

What is your primary concern regarding the potential myelofibrosis readout? How are you addressing simultaneous readouts in both myelofibrosis and endometrial cancer? - Edward Andrew Tenthoff (Piper Sandler)

2025Q2: We do not expect any meaningful changes to Selinexor's current sales force. - Richard A. Paulson(CEO)

Contradiction Point 2

Impact of Baseline TSS on Results

It affects expectations regarding the potential outcomes and efficacy of the myelofibrosis pivotal combo study, which is critical for regulatory approval and market acceptance.

How will baseline TSS affect read-through from Phase I to Phase III, and what are your thoughts on activity based on platelet count? - Colleen Hanley (Robert W. Baird & Co. Incorporated, Research Division)

2025Q3: Encouraged by the baseline TSS of 22.5, suggesting potential improvement over ruxolitinib alone. - Reshma Rangwala(CMO)

Can you explain the higher TSS at baseline in the pivotal MF combo study and how this affects the study's outcomes? - Colleen Margaret Kusy (Baird)

2025Q2: Higher baseline TSS can positively impact meaningful outcomes, such as achieving a 50% improvement or a greater average reduction in TSS. - Reshma Rangwala(CMO)

Contradiction Point 3

Myelofibrosis Study Enrollment

It involves the timeline and expectations for the completion of patient enrollment in the SENTRY study, which is a critical milestone for the company's myelofibrosis development program.

What level of detail will myelofibrosis data include in 2026, including SVR, TSS, and OS trends, and will it be presented across medical meetings? - Peter Lawson (Barclays Bank PLC, Research Division)

2025Q3: We expect to report top line results in the second half of 2026, with data potentially presented at an upcoming medical meeting. - Reshma Rangwala(Executive VP, Chief Medical Officer & Head of Research)

Can you explain your assumptions for achieving full enrollment in June and July? - Unidentified Analyst (Jefferies)

2025Q1: We now expect enrollment to be completed between June and July. - Reshma Rangwala(Chief Medical Officer & Head, Research)

Contradiction Point 4

Selinexor Dose and Anti-emetics

It pertains to the use of different doses of selinexor and the integration of learnings from multiple myeloma about the use of dual antiemetics, which can impact patient outcomes and tolerability.

What lessons from multiple myeloma can inform the commercial launch potential in myelofibrosis? - Jonathan Chang(Leerink Partners LLC, Research Division)

2025Q3: Learnings from multi myeloma include lower selinexor doses and use of dual antiemetics. - Richard Paulson(CEO)

Can you explain the characteristics of dMMR patients ineligible for checkpoint inhibitors and any efficacy differences? - Unidentified Analyst(RBC Capital Markets)

2024Q4: The lower Selinexor dose and anti-emetics improve safety. - Reshma Rangwala(CMO)