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Karyopharm Therapeutics Inc. (KPTI)·Q2 2025 Earnings Summary

Executive Summary

  • Q2 2025 revenue was $37.9M, essentially in line with S&P Global consensus ($37.93M actual vs $37.93M estimate), while GAAP diluted EPS of -$4.32 was a slight miss versus -$4.03 consensus; U.S. XPOVIO net product revenue rose 6% YoY to $29.7M as gross-to-net normalized post Q1 returns . EPS/Revenue consensus from S&P Global Estimates.*
  • Guidance: Total revenue guidance reaffirmed at $140–$155M; U.S. XPOVIO net product revenue guidance lowered to $110–$120M (from $115–$130M in Q1); R&D+SG&A guidance narrowed to $240–$250M .
  • Liquidity and strategic review: Cash and investments fell to $52.0M at 6/30/25; management is “exploring financing transactions and strategic alternatives” ahead of $24.5M notes maturing Oct 2025 and a $25M minimum liquidity covenant .
  • Pipeline: SENTRY (MF) screening/ enrollment entering final stages in Q2 and later completed post-quarter (Sept 10); blinded safety suggests improved tolerability; top-line now expected March 2026—key stock catalyst alongside financing outcome .

What Went Well and What Went Wrong

  • What Went Well

    • XPOVIO commercial resilience: U.S. net product revenue grew to $29.7M (+6% YoY); community setting remained ~60% of revenue .
    • Gross-to-net normalization: GTN provisions fell to 26.8% in Q2 from 45% in Q1, reverting toward historical levels; management expects relative consistency through year-end .
    • Pipeline momentum and tolerability: CEO: “we are in our final weeks of enrolling our Phase 3 SENTRY trial” with top-line in March 2026 ; CMO highlighted blinded safety suggesting lower grade ≥3 anemia vs historical ruxolitinib and materially reduced vomiting due to mandated dual antiemetics in first two cycles .

  • What Went Wrong

    • Mix-driven top-line pressure: License and other revenue fell to $8.2M from $14.8M YoY due to a $6.0M non-recurring license item in Q2’24 .
    • P&L drag from capital structure: Interest expense rose to $11.2M from $8.9M YoY and other expense swung unfavorable vs Q2’24 due to 2024 refinancing-related fair value items; GAAP net loss was -$37.3M .
    • Liquidity overhang: Cash and investments fell to $52.0M; company is actively exploring financing/strategic alternatives amid near-term note maturity and covenant constraints—an investor concern into H2’25 .

Financial Results

P&L highlights (reported)

MetricQ4 2024Q1 2025Q2 2025
Total Revenue ($M)$30.5 $30.0 $37.9
Net (Loss) Income ($M)-$30.8 -$23.5 -$37.3
Diluted EPS ($)-$3.60* (S&P actual; PR shows -$0.24 pre-split)-$2.77 -$4.32

Q2 2025 vs S&P Global consensus

MetricEstimateActualBeat/Miss
Revenue ($M)$37.93*$37.93 In-line
Primary EPS ($)-$4.03*-$4.32 Miss (~$0.29)

Revenue mix

Revenue ($M)Q2 2024Q1 2025Q2 2025
Net Product (U.S. XPOVIO)$28.0 $21.1 $29.7
License & Other$14.8 $9.0 $8.2
Total$42.8 $30.0 $37.9

Margins (S&P Global calculations)

MarginQ4 2024Q1 2025Q2 2025
Gross Margin %455.6%*-19.7%*10.8%*
EBITDA Margin %-102.2%*-110.5%*-64.1%*
Net Income Margin %-100.8%*-78.2%*-98.2%*

KPIs and balance sheet

KPIQ2 2024Q1 2025Q2 2025
Gross-to-Net (GTN)29.3% 45.0% 26.8%
Community mix of U.S. XPOVIO revenue~60% —~60%
Royalty Revenue ($M)1.3 (implied, YoY base)1.7 1.6
Interest Expense ($M)$8.9 $11.0 $11.2
Cash & Investments ($M, period-end)$133.9 (9/30/24) $70.3 (3/31/25) $52.0 (6/30/25)

Notes: Asterisks denote values retrieved from S&P Global.*

Guidance Changes

MetricPeriodPrevious Guidance (Q1 2025)Current Guidance (Q2 2025)Change
Total RevenueFY 2025$140M–$155M $140M–$155M Maintained
U.S. XPOVIO Net Product RevenueFY 2025$115M–$130M $110M–$120M Lowered
R&D + SG&AFY 2025$240M–$255M $240M–$250M Narrowed lower end
Liquidity runway (qualitative)2025–26Into early Q4’25 including note and covenant effects To Oct 15, 2025 note maturity; excluding note and covenant, into Jan 2026 Updated language/clarity

Earnings Call Themes & Trends

TopicPrevious Mentions (Q4 2024, Q1 2025)Current Period (Q2 2025)Trend
Myelofibrosis (SENTRY)Endpoint updated to Abs-TSS; target N~350; H2’25 topline initially Screening closing; blinded safety suggests lower grade ≥3 anemia and lower vomiting with mandated antiemetics; topline March 2026 Positive execution; timing clarified later
Endometrial cancer (EC-042)Focused enrollment on TP53 WT pMMR/ dMMR ineligible; topline mid-2026 Enrollment “steady”; still targeting 2026 topline Steady
Multiple Myeloma (XPORT-MM-031)Enrollment completed ~120; topline 1H 2026 Continuing follow-up; 1H 2026 topline reiterated Steady
Commercial executionDemand growth late 2024; GTN headwinds GTN normalized to 26.8%; community ~60% mix; royalty +28% YoY Improving margin dynamics
Financing/strategic alternativesLiquidity flagged; exploring runway extension Active engagement with lenders/advisors; exploring full range of options (Centerview) Heightened focus

Management Commentary

  • CEO Richard Paulson: “We are operating in a period of financial constraints with a near term debt maturity in October. We are actively engaged with our lenders and advisors to enhance our liquidity and maximize value… we delivered solid commercial results and made exciting progress towards enrolling our pivotal Phase III trials” .
  • CMO Reshma Rangwala on tolerability: “The extrapolated rate of grade 3/4 anemia [~26%] for the combination is meaningfully lower than the ~37% historically reported for ruxolitinib… vomiting fell from ~50% in Phase 1 to ~10–12% with mandated dual antiemetics” .
  • CFO Lori Macomber: “Gross to net provisions for XPOVIO in the second quarter were 26.8%, down from 45% in Q1 and 29.3% in Q2 2024… We announced a roughly 20% reduction in our workforce in early July… expected to lower annual spend by approximately $13M” .
  • Press release framing: “Reaffirms full-year 2025 total revenue guidance of $140–$155M; updates U.S. XPOVIO net product revenue guidance to $110–$120M” .

Q&A Highlights

  • Myelofibrosis outlook and risk: Management emphasized confidence in combination efficacy (SVR35 and absolute TSS) and potential disease modification; acknowledged symptom improvement as a field challenge but cited 18.5-point Abs-TSS in Phase 1 and blinded safety trends in Phase 3 .
  • Tolerability drivers: Marked reduction in nausea/vomiting attributed to required dual antiemetics in first two cycles (>90% adherence) and mechanistic effects; FDA alignment on endpoints unchanged since 2024 .
  • Revenue drivers: Inventory remained consistent; improvement driven by GTN normalization and steady demand .
  • SENTRY-2 protocol: Plans to amend to broaden platelet eligibility, aiming to improve enrollment; bar for success in moderate thrombocytopenia cohort ~25–30% vs ~15% historical .
  • Liquidity pathway: Company exploring full range of financing and strategic alternatives; no further details until Board decisions .

Estimates Context

  • Q2 2025 results vs S&P consensus: Revenue in-line ($37.93M vs $37.93M) and EPS a modest miss (-$4.32 vs -$4.03). 6 revenue and 5 EPS estimates contributed to consensus.*
  • FY 2025 setup: Company’s total revenue guidance ($140–$155M) brackets S&P revenue consensus ($147.8M), while lowered XPOVIO guide ($110–$120M) may nudge product-mix expectations lower near term; operating expense actions (20% workforce reduction) could support out-year margin trajectories pending financing outcomes . Values retrieved from S&P Global.*

Key Takeaways for Investors

  • Core commercial stabilized: XPOVIO U.S. revenue rose 6% YoY with GTN provisions normalizing to 26.8%, supporting Q2 in-line revenue despite license revenue headwinds .
  • Guidance signals modest recalibration: Total revenue held, but XPOVIO guide trimmed to $110–$120M—watch H2 trend in demand and GTN sustainability .
  • Liquidity is the near-term swing factor: $52M cash at 6/30 and October note maturity drive urgency around financing/strategic alternatives; outcomes here likely dictate stock path ahead of clinical readouts .
  • SENTRY is the transformational catalyst: Enrollment milestones achieved and topline now guided for March 2026; blinded safety trends and prior Phase 1 efficacy underpin potential for standard-of-care shift if positive .
  • Expense discipline underway: ~20% workforce reduction expected to reduce annual spend by ~$13M in 2026, with benefits starting in Q4 2025 reporting .
  • Estimate implications: Minimal change to FY revenue consensus likely; EPS path still constrained by interest expense and non-cash items until capital structure is addressed. Values retrieved from S&P Global.*

Additional detail and source references

  • Q2 2025 press release and 8-K financial details, segment mix, costs, and guidance .
  • Q2 2025 earnings call transcript for GTN normalization, expense actions, blinded safety/tolerability, and liquidity strategy .
  • Q1 2025 press release for prior-quarter comps and initial 2025 guidance .
  • Q4 2024 press release for baseline comps and endpoint update history .
  • Post-quarter press release: SENTRY enrollment completion and March 2026 topline timing .

Notes: Asterisks denote values retrieved from S&P Global.