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Karyopharm Therapeutics Inc. (KPTI)·Q4 2024 Earnings Summary

Executive Summary

  • Q4 2024 revenue was $30.5M with U.S. XPOVIO net product revenue of $29.3M; product revenue grew 16% YoY (vs. $25.1M in Q4 2023), while total revenue declined on lower license/other revenue .
  • 2025 initial guidance: total revenue $140–$155M; U.S. XPOVIO $115–$130M; R&D+SG&A $240–$255M; cash runway into Q1 2026 (Q4 2025 including debt repayment/min liquidity covenant) .
  • Clinical pivots: SENTRY Phase 3 in myelofibrosis remains on track (enrollment completion 1H25; topline 2H25). Endometrial Phase 3 EC-042 is refocused on TP53 wt pMMR (plus dMMR ineligible for CPI), sample size increased to ~276, pushing topline to mid-2026—an important narrative shift for the franchise .
  • Street comparisons: S&P Global consensus could not be retrieved at time of writing; as a result, beat/miss vs. estimates cannot be assessed (S&P Global data unavailable).

What Went Well and What Went Wrong

What Went Well

  • U.S. XPOVIO execution: Q4 net product revenue rose to $29.3M (+16% YoY) with steady demand in H2 across community (~60% of mix) and academic settings; management emphasized resilient demand despite an intensified competitive landscape .
  • Cost discipline: SG&A fell to $27.2M in Q4 from $30.7M YoY; full-year R&D+SG&A landed toward the low end of the narrowed FY24 guidance, reflecting ongoing cost optimization .
  • Clear 2025 catalysts and confidence: “In 2025, our teams remain focused on the transformative opportunity to redefine the standard of care in myelofibrosis,” positioning a potentially rapid launch if approved .

What Went Wrong

  • Mix headwind: License/other revenue declined to $1.3M in Q4 (vs. $8.7M YoY), pulling total revenue down despite stronger product sales .
  • Gross-to-net pressure: Q4/XFY gross-to-net rose to 33.3%/30.9% (vs. 23.5%/22.3% in 2023), driven primarily by increased 340B discounts and Medicare rebates—constraining net revenue conversion .
  • EC-042 timing push: Trial design modifications (focus on pMMR and dMMR CPI-ineligible) increased sample size to ~276 and moved topline to mid-2026, extending timelines for second major catalyst beyond SENTRY .

Financial Results

MetricQ2 2024Q3 2024Q4 2024
Total Revenue ($M)$42.8 $38.8 $30.5
U.S. XPOVIO Net Product Revenue ($M)$28.0 $29.5 $29.3
License & Other Revenue ($M)$14.8 $9.3 $1.3
Loss from Operations ($M)-$28.1 -$26.3 -$31.3
Net Income (Loss) ($M)$23.8 -$32.1 -$30.8
Basic EPS ($)$0.15 -$0.26 -$0.24

Segment/mix (revenue components):

MetricQ2 2024Q3 2024Q4 2024
Net Product Revenue ($M)$28.0 $29.5 $29.3
License & Other Revenue ($M)$14.8 $9.3 $1.3

Key KPIs and operating items:

KPIQ2 2024Q3 2024Q4 2024
Cash, Cash Equivalents & Investments ($M, period-end)$152.1 $133.5 $108.7
R&D Expense ($M)$38.4 $36.1 $33.3
SG&A Expense ($M)$31.1 $27.6 $27.2
Interest Expense ($M)$8.9 $11.4 $11.2
Gross-to-Net Discount (%)N/AN/A33.3% (Q4); FY24: 30.9%

Notes: Q4 YoY XPOVIO net product revenue +16% ($29.3M vs. $25.1M) . Total revenue YoY decline reflects lower license/other revenue .

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
Total RevenueFY 2025N/A (initial)$140–$155M Initial
U.S. XPOVIO Net Product RevenueFY 2025N/A (initial)$115–$130M Initial
R&D + SG&A ExpensesFY 2025N/A (initial)$240–$255M Initial
Cash RunwayThroughInto Q1 2026 (excl. notes/min liquidity into Q4 2025) ReiteratedMaintained

Earnings Call Themes & Trends

TopicQ2 2024 (Prev-2)Q3 2024 (Prev-1)Q4 2024 (Current)Trend
Myelofibrosis SENTRY (endpoint/enrollment)On track for 2H25 topline; strong mechanistic/preclinical rationale FDA alignment to Abs‑TSS co-primary; sample size ~350; topline 2H25 On track: complete enrollment 1H25; topline 2H25; endpoint rationale reiterated Execution progressing; confidence rising
Endometrial EC‑042 design/timingTopline early 2026 due to higher screen failures Topline early 2026; SIENDO subgroup data supportive Focus on TP53 wt pMMR/dMMR-ineligible; n≈276; topline mid‑2026 Narrowed population; timeline pushed
XPOVIO commercial performance$28.0M; QoQ growth; ex‑US reimbursement wins $29.5M; demand growth community/academic $29.3M; consistent demand H2; community ~60% of revenue Stable to improving demand; resilient vs competition
Gross-to-net dynamicsNot quantifiedHigher QoQ gross‑to‑net from 340B mix Q4 33.3%; FY24 30.9%; headwind from 340B/Medicare Elevated vs 2023; monitoring
Financing/runwayRefinancing extended maturities to 2028/2029 Liquidity into Q1’26 (Q4’25 incl. debt/covenant) Runway reiterated; exploring financing/BD to extend Adequate near-term; potential overhang
MM SPd (XPORT‑MM‑031)Design amendments; potential topline 1H25 Target n≈120; pending update Enrollment completed ~120; pending regulatory engagement Closer to update decision point

Management Commentary

  • “In 2025, our teams remain focused on the transformative opportunity to redefine the standard of care in myelofibrosis… and leveraging our demonstrated commercialization capabilities in multiple myeloma to support a rapid launch, subject to approval.” — CEO Richard Paulson .
  • “The gross to net discount for XPOVIO in the fourth quarter and full year 2024 was 33.3% and 30.9%… primarily driven by 340B utilization and Medicare rebates. We expect the gross to net discount to be similar in 2025 to 2024.” — CFO Lori Macomber .
  • “We… aligned with the FDA last year on a change in our co-primary endpoint to absolute TSS. This was a very favorable change that we believe increases the probability of success of our Phase III SENTRY trial.” — CEO Richard Paulson .
  • “We are modifying the design of our Phase 3 XPORT-EC-042 trial… focus on TP53 wild-type pMMR or dMMR medically ineligible… increasing the trial sample size to ~276… topline mid-2026.” — Company update .

Q&A Highlights

  • SENTRY Abs‑TSS buffer/statistical context: Mgmt believes a 3–4+ point delta is achievable; prior Phase 3 showed significance with ~2‑point difference, supporting power assumptions, though specific SENTRY stats not disclosed .
  • EC-042 FDA dialogue: Shift driven by evolving SoC (CPI for all MMR statuses) and modest CPI benefit in pMMR; FDA recommended focus on pMMR; SIENDO subgroup data (TP53 wt) viewed as supportive .
  • SENTRY enrollment/baseline comparability: Patient characteristics tracking Phase 1 and contemporary Phase 3 MF trials; discontinuation/dose modifications tracking expectations (blinded) .
  • Symptom endpoint excluding fatigue: Primary Abs‑TSS analysis excludes fatigue (consistent with precedent); FDA aligned; fatigue can be analyzed later .
  • Cash runway/financing: Company evaluating BD, alliances, debt extension, or equity to extend runway through key readouts while maintaining discipline .

Estimates Context

  • Wall Street consensus from S&P Global for Q4 2024 revenue and EPS was unavailable at the time of analysis due to access limits; therefore, we cannot assess beat/miss vs. estimates. Estimates may need to adjust for: (1) persistent gross‑to‑net pressure; (2) lower license/other revenue in Q4; (3) 2025 guide midpoint implying ~flat total revenue vs 2024 but +~11% midpoint growth in U.S. XPOVIO .

Key Takeaways for Investors

  • XPOVIO demand remains resilient; Q4 net product revenue rose 16% YoY to $29.3M, though total revenue fell on softer license/other, underscoring sensitivity to non‑product contributions .
  • Elevated gross‑to‑net (Q4 33.3%, FY24 30.9%) is now a structural headwind; 2025 gross‑to‑net expected similar to 2024, with typical seasonal 1Q step-up .
  • 2025 guide frames a year of execution: total revenue $140–$155M and U.S. XPOVIO $115–$130M; cost base trending down with R&D+SG&A $240–$255M .
  • Primary stock catalyst: SENTRY topline in 2H25; enrollment completion in 1H25 could be an interim sentiment driver. A clear, positive Abs‑TSS/SVR35 outcome could be transformational for valuation and launch setup .
  • EC-042’s narrowed design enhances regulatory clarity but moves topline to mid‑2026; defers the second major catalyst and concentrates near-term focus on MF readout .
  • Balance sheet adequate into Q1’26 (Q4’25 including notes/covenant), but management is actively evaluating financing/BD options—this remains a potential overhang until addressed .
  • For near-term trading, watch: updates on SENTRY enrollment completion, any SENTRY‑2 (MF monotherapy) data subset in 1H25, and cadence on gross‑to‑net/340B dynamics that affect quarterly revenue prints .

Appendix: Additional Detail

  • Q4 detail: Total revenue $30.5M; product $29.3M; license/other $1.3M; cost of sales $1.3M; R&D $33.3M; SG&A $27.2M; interest expense $11.2M; net loss $30.8M .
  • FY24: Total revenue $145.2M; U.S. XPOVIO $112.8M; cash/cash equivalents/restricted/investments $109.1M at year-end .

Sources:

  • Q4 2024 press release and financials .
  • 8‑K (Item 2.02) incorporating press release .
  • Q4 2024 earnings call transcript (prepared remarks and Q&A) .
  • Prior quarters: Q3 and Q2 2024 press releases ; .

S&P Global consensus data was unavailable at time of writing; beat/miss vs. consensus could not be assessed.