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Karyopharm Therapeutics Inc. (KPTI)·Q3 2025 Earnings Summary

Executive Summary

  • Q3 delivered $44.0M total revenue (+13% YoY) with U.S. XPOVIO net product revenue of $32.0M (+8.5% YoY); S&P Global consensus was $42.4M revenue and ($3.52) EPS, so revenue was above but EPS ($3.82) was below; the EPS delta was driven largely by below-the-line, mostly non-cash items (mark-to-market, interest) while operating loss improved ~42% YoY . Revenue consensus and EPS consensus from S&P Global*.
  • Full-year 2025 guidance reaffirmed for total revenue ($140–$155M) and U.S. XPOVIO ($110–$120M); R&D+SG&A lowered to $235–$245M (from $240–$250M), reinforcing cost discipline .
  • Balance sheet strengthened via October financing/deferrals (~$100M flexibility), extending cash runway into Q2 2026; Q3 cash and investments were $46.2M, ~$78M on a pro forma basis after the October transactions .
  • Key 2026 catalyst: SENTRY (MF) Phase 3 top-line expected March 2026; enrollment completed (n=353) and blinded safety snapshot trends (lower extrapolated Grade 3/4 anemia vs ruxolitinib) underpin management confidence .

What Went Well and What Went Wrong

What Went Well

  • U.S. XPOVIO net product revenue grew to $32.0M (+8.5% YoY), as community channels (~60% mix) remained the core driver and gross-to-net stayed favorable (27%) .
  • Operating loss improved to ($15.2M) from ($26.3M) YoY (~42% improvement) on lower R&D and SG&A, reflecting cost reductions and resource prioritization .
  • Strategic financing extended runway into Q2 2026; management highlighted “strengthened financial foundation” and readiness for potential MF launch pending data and approvals .

Quotes:

  • “This has been a very productive quarter as we have strengthened our financial foundation…” – Richard Paulson, CEO .
  • “Gross to net provisions for XPOVIO were 27% in the third quarter… and [we] expect [them] to remain relatively consistent in Q4 2025.” – CFO .

What Went Wrong

  • GAAP EPS of ($3.82) was below S&P Global consensus ($3.52), with more than half of the net loss driven by below-the-line, largely non-cash interest and mark-to-market remeasurements . EPS consensus from S&P Global.
  • Other (expense) swung to ($7.4M) vs $3.8M other income in Q3’24 due to recurring non-cash fair value remeasurements tied to prior refinancing .
  • Balance sheet remains leveraged with sizable liabilities and a stockholders’ deficit, despite improved liquidity outlook post-October transactions .

Financial Results

MetricQ3 2024Q2 2025Q3 2025
Total Revenue ($M)$38.783 $37.929 $44.044
U.S. XPOVIO Net Product Revenue ($M)$29.516 $29.681 $32.032
License & Other Revenue ($M)$9.267 $8.248 $12.012
Loss from Operations ($M)($26.283) ($24.387) ($15.220)
Interest Expense ($M)$11.385 $11.228 $11.008
Other (Expense) Income ($M)$3.792 ($2.210) ($7.418)
GAAP Net Loss ($M)($32.072) ($37.252) ($33.127)
GAAP EPS($3.85) ($4.32) ($3.82)

Vs. Estimates (S&P Global):

MetricConsensusActualResult
Revenue ($M)$42.411*$44.044 Above
GAAP EPS($3.52)*($3.82) Below

Values with asterisk (*) retrieved from S&P Global.

Segment/line items:

Segment/LineQ3 2024Q2 2025Q3 2025
U.S. XPOVIO Net Product Rev ($M)$29.516 $29.681 $32.032
License & Other Rev ($M)$9.267 $8.248 $12.012
Cost of Sales ($M)$1.300 $1.051 $2.113
R&D ($M)$36.134 $32.788 $30.544
SG&A ($M)$27.632 $28.477 $26.607

KPIs and Operating Metrics:

KPIQ3 2024Q2 2025Q3 2025
Gross-to-net % (XPOVIO)31% 26.8% 27%
Royalty Revenue ($M)$0.9 $1.6 $1.5
Community Mix of U.S. Net Product Rev~60% ~60% ~60%
Cash, cash equivalents, restricted cash & investments ($M)—$52.0 (6/30/25) $46.2 (9/30/25); ~$78 pro forma post-Oct financing

Notes: Q4 license/other mix expected to be primarily royalties; no significant additional Q4 milestones anticipated .

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
Total RevenueFY 2025$140–$155M (Aug 11, 2025) $140–$155M (Nov 3, 2025) Maintained
U.S. XPOVIO Net Product RevenueFY 2025$110–$120M (Aug 11, 2025) $110–$120M (Nov 3, 2025) Maintained
R&D + SG&AFY 2025$240–$250M (Aug 11, 2025) $235–$245M (Nov 3, 2025) Lowered
Liquidity/Cash RunwayCorporateTo notes maturity Oct-2025; into Jan-2026 excl. notes Into Q2 2026 post Oct financing Improved
Q4 License/Other MixQ4 2025—Primarily royalties; no significant milestones expected Clarified

Earnings Call Themes & Trends

TopicPrevious Mentions (Q1 & Q2 2025)Current Period (Q3 2025)Trend
SENTRY (MF) enrollment & endpointsPassed futility; ~80% enrolled; switching to absolute TSS (excluding fatigue); MMRM planned Enrollment completed (n=353); topline March 2026; reiterated co-primaries SVR35 & absolute TSS Positive execution/unchanged timing
Blinded safety (MF)Extrapolated lower Grade 3/4 anemia vs ruxolitinib; low TEAE discontinuations; antiemetic protocol emphasized Extrapolated Grade 3/4 anemia ~26% vs ~37% historical ruxolitinib; discontinuations ~5–7% Confidence building
Commercial XPOVIO dynamicsCommunity ~60% mix; demand consistent; royalty growth Community ~60%; royalty $1.5M vs $0.9M YoY; GTN 27% Stable demand, improving GTN
Financing/liquidityExploring financing/strategic alternatives $100M flexibility/deferrals; runway into Q2 2026 Improved
Ex-US strategyPartners active; more launches; exploring options Partners engaged; Japan remains unpartnered Stable/clarified
Endometrial cancer EC-042Enrollment ongoing; top-line mid-2026 Enrollment ongoing; top-line mid-2026 Unchanged
Myeloma EMN29Enrollment complete (Q4’24); top-line 1H26 Continue patient follow-up; top-line 1H26 Unchanged
Peak MF opportunityU.S. peak up to ~$1B; 75% prescriber intent to use combo Reiterated ~$1B opportunity; prescriber intent; 13-mo real-world DoT baseline Unchanged/validated messaging

Management Commentary

  • CEO: “This has been a very productive quarter… strengthened our financial foundation and made meaningful clinical progress with enrollment completion of our Phase 3 SENTRY trial…” .
  • CMO: “The extrapolated rate of Grade 3/4 anemia for the combination is ~26%, meaningfully lower than the ~37% historically reported for ruxolitinib… discontinuation ~5–7%” .
  • CCO: “75% of U.S. physicians showed an intent to treat with combination therapy based on third-party market research” .
  • CFO: “More than half of [Q3 net loss] is driven by below-the-line items… interest expense is almost entirely non-cash at this point, and the $7.4M of non-cash mark-to-market” .

Q&A Highlights

  • MF readout: Top-line in March 2026 will report co-primaries (SVR35, absolute TSS) and safety; additional secondaries may come later at conferences .
  • Commercial build: Strong overlap with current MM footprint; minimal additions anticipated; partners to drive ex-U.S.; Japan remains unpartnered .
  • Baseline TSS: Mean baseline absolute TSS (excluding fatigue) ~22.5 in SENTRY; management views as favorable for detecting symptom improvement .
  • Safety/tolerability drivers: Dual antiemetics mandatorily used in first two cycles in Phase 3, reducing nausea/vomiting vs Phase 1; supports better tolerability .
  • Q4 revenue mix: License/other in Q4 to be primarily royalties; no significant additional milestones expected .
  • Financing triggers: No warrants/milestones tied to MF data that would automatically extend capital; improved liquidity already achieved via October transactions .

Estimates Context

  • Revenue beat: Actual $44.0M vs consensus $42.4M*; EPS miss: actual ($3.82) vs consensus ($3.52)* . Revenue consensus and EPS consensus from S&P Global*.
  • Estimate revisions: CFO guided that Q4 license/other will be mostly royalties (no significant milestones), which could temper sell-side Q4 “other revenue” expectations .

Values with asterisk (*) retrieved from S&P Global.

Key Takeaways for Investors

  • Core print: Clean top-line beat with improving operating loss and disciplined OpEx; EPS below consensus driven by largely non-cash items—less concerning for fundamentals .
  • Guidance: Reaffirmed revenue ranges; OpEx lowered—supports improving operating trajectory into 2026 .
  • Liquidity: October financing/deferrals extend runway into Q2 2026, de-risking near-term funding ahead of pivotal readouts .
  • Commercial: XPOVIO is steady (community ~60%, GTN 27%); ex-U.S. royalties growing; Q4 “other” to be primarily royalties—model conservatively for milestones .
  • Pipeline setup: SENTRY MF topline in March 2026 is the major stock catalyst; EMN29 (MM) 1H26 and EC-042 (EC) mid-2026 provide stacked optionality .
  • Risk watch: Balance sheet leverage/stockholders’ deficit and continued non-cash fair value swings can add EPS volatility; going-concern language persists in filings .
  • Trading lens: Positive revenue beat/cost control vs EPS optics; focus on 2026 MF catalyst path, baseline/safety setup, and liquidity extension as supports for sentiment near-term .

Footnote: All share and per-share figures reflect the 1-for-15 reverse split effected on February 25, 2025 .

*Values retrieved from S&P Global.