Karyopharm Therapeutics Inc. (KPTI) Earnings

Management highlights

- Corporate Priorities and Milestone Progress * The company entered 2026 with three core priorities: advancing late-stage clinical programs, maintaining the commercial foundation of Expovio in multiple myeloma, and operating with financial discipline approaching key value-driving milestones. * Meaningful progress was achieved since Q4 2025: the Phase III Sentry trial in frontline myelofibrosis (MF) reported positive top-line results, enrollment completed in the Phase III export EC042 trial in endometrial cancer (EC), and the balance sheet was strengthened via Q1 2026 financing. * Current focus: advancing regulatory and scientific engagement for the Sentry trial, preparing for EC042 top-line data readout, and maintaining financial discipline. - Sentry Trial (Selinexor + Ruxolitinib for Frontline Myelofibrosis) Clinical Results * The combination demonstrated a compelling differentiated profile: rapid, deep, and sustained spleen volume responses, a promising overall survival (OS) signal, and evidence of potential disease modification via greater variant allele frequency (VAF) reductions as early as week 24, addressing a major unmet need where only JAK inhibitor monotherapy is approved. * Top-line results: co-primary endpoint SVR35 (spleen volume reduction ≥35%) at week 24 was 50% for the combination vs. 28% for Ruxolitinib alone (p<0.0001, statistically significant). The second co-primary endpoint of symptom improvement at week 24 did not reach statistical significance, with both arms experiencing meaningful baseline improvement. * Key positive signals: the combination yielded an OS hazard ratio of 0.43 (nominal p=0.0222), the first potential frontline MF treatment to show an OS improvement over standard of care. 32% of combination arm patients achieved ≥20% VAF reduction, indicating potential disease modification. The safety profile was generally manageable, with no new signals, and improved tolerability versus the Phase I study due to lower Selinexor dosing and mandatory dual antiemetics. * Next steps: full data will be presented as a late-breaking oral presentation at ASCO, with peer-reviewed publication expected mid-2026, followed by ongoing FDA engagement. - export EC042 Trial (Selinexor Maintenance for P53 Wild-Type Endometrial Cancer) Progress * This is a biomarker-driven program targeting P53 wild-type, mostly MMR-proficient (PMMR) endometrial cancer, a population with no approved personalized biomarker-driven maintenance therapy and limited benefit from current checkpoint inhibitor-based regimens, representing ~50% of all EC patients. Molecular classification of EC is already standard of care, supporting rapid real-world adoption if approved. * Enrollment completed with 257 patients in the intent-to-treat (ITT) population and ~220 patients in the modified intent-to-treat (MITT, primary analysis) population, which is largely composed of the target P53 wild-type PMMR subgroup. Top-line data remains on track for mid-2026. * Dose and supportive care were optimized versus earlier studies: Selinexor is dosed at 60mg once weekly (vs 80mg in the prior Siendo trial) with mandatory dual antiemetics for the first two cycles, expected to improve tolerability and allow longer treatment duration. Prior Siendo trial data in this subgroup showed strong, deepening progression-free survival (PFS) benefit over time: median PFS of 28.4 months overall (HR 0.44) and approaching 40 months for P53 wild-type PMMR patients (HR 0.36), which compares very favorably to existing standard of care data. - Commercial Readiness and Opportunity * Expovio is well-positioned in multiple myeloma: focused on the community setting (60% of U.S. sales) where it is valued as a flexible oral option for 2nd-4th line treatment, and has a differentiated mechanism that allows use before CAR-T and in patients progressing on T-cell engaging therapies. * Potential new indications offer meaningful commercial opportunity: the U.S. frontline MF market has ~7,000 newly diagnosed patients annually, ~4,000 addressable, with peak U.S. revenue potential of ~$1 billion. The target EC population has ~17,000 newly diagnosed advanced/recurrent patients annually, representing a significant opportunity in a multibillion-dollar market. 70% of MF patients and a large share of EC patients are treated in the community setting, which aligns with the company's existing commercial footprint. * The company already has established, experienced capabilities across sales, marketing, market access, and medical affairs, allowing launch preparation with minimal incremental pre-approval investment and only modest additional post-launch spending. Both new indications are in concentrated treatment landscapes with high unmet need, supporting rapid adoption if approved.

Guidance

- The company reaffirmed its full-year 2026 guidance, with no upward or downward revision from prior outlooks. - Total full-year 2026 revenue is expected to be in the range of $130 million to $150 million. - U.S. Expovio net product revenue for full-year 2026 is expected to be $115 million to $130 million, with all remaining license and other revenue consisting of royalties over the final three quarters of the year. - Combined full-year 2026 R&D and SG&A expenses are expected to be in the range of $230 million to $245 million. - Based on the current operating plan, existing cash liquidity is sufficient to fund operations into late Q3 2026.

Segment performance

The only commercial product segment at this time is U.S. Expovio for multiple myeloma. Total company revenue for Q1 2026 was $35.1 million, compared to $30.0 million in Q1 2025. U.S. Expovio net product revenue was $29.2 million, compared to $21.1 million in the prior year quarter. Expovio net product revenue represented 83.2% of total Q1 2026 revenue. The year-over-year increase in Expovio revenue was driven by an improvement in gross-to-net dynamics (21.8% in Q1 2026 vs. 45% in Q1 2025, which included an atypical product return adjustment in the prior year), resulting in ~26% underlying growth to net. Underlying Expovio demand was lower than Q1 2025 due to new competitive entrants, which the company has experience navigating. Research and development (R&D) expenses were $33.8 million, and selling, general & administrative (SG&A) expenses were $26.7 million, both consistent with year-ago levels. The company reported a net loss of $22.4 million for Q1 2026, compared to a $23.5 million net loss in Q1 2025, with a 20% reduction in operating loss driven by higher revenue and cost discipline. The company ended the quarter with $91.2 million in total cash, cash equivalents, and restricted cash, including $50 million raised via Q1 2026 financing.

Risks & headwinds

- Underlying demand for Expovio has declined due to new competitive entry in the multiple myeloma market, creating pressure on the core commercial revenue base. - Positive top-line results from the Sentry trial do not guarantee regulatory approval, compendia inclusion, or commercial success, as FDA review can result in unexpected delays or rejection even with positive clinical data. - There is no guarantee that the EC042 trial will replicate the strong PFS benefit observed in the earlier Siendo trial, even with optimized dosing and supportive care. Enrollment in the ITT population was slightly lower than originally planned, though the company states the trial remains adequately powered for its primary endpoint. - Clinical trial results are subject to unexpected safety signals or outcome changes as follow-up matures, which could alter the risk-benefit profile of Selinexor in both indications. - The company currently only has enough cash to fund operations into late Q3 2026, requiring additional financing to extend the runway beyond that point, which may not be available on favorable terms or at all.

Analyst Q&A

• Q: Have you done additional analysis of deaths in the Sentry trial's control arm, and what should we expect beyond the initial top-line ASCO data?

  A: Management confirmed the team is reviewing the 23 reported deaths from the top-line cutoff. They noted the distribution and causes of death are entirely consistent with expectations for MF and oncology trials, with most deaths attributed to disease progression and adverse events, and no unexpected outlying trends. Additional granular data will be presented at future medical congresses as analysis continues.

• Q: What is the timing of FDA engagement for Sentry, and what can we expect for the regulatory path?

  A: Management noted the FDA has been a collaborative partner from the start of the Sentry trial. They highlighted that what makes the Sentry data unique is the combination of spleen responses, a promising early overall survival signal, and evidence of disease modification via rapid VAF reduction, which they believe makes the profile compelling for regulators. No specific timing for a meeting or submission was provided, but the company plans to share updates on next steps over the next two quarters.

• Q: What are the gating factors for compendia inclusion of Selinexor for MF, and what is the revenue opportunity of inclusion without full approval?

  A: Management noted compendia bodies like NCCN are independent and regularly update guidelines based on presented and published clinical data. The company expects the ASCO presentation and mid-2026 peer-reviewed publication will lead to guideline review, with potential inclusion if the data is deemed compelling. In the high unmet need MF landscape, historical precedent shows products with compendia listing can achieve approximately 50% of the peak revenue they would generate with full approval, even without an active label, as physicians can elect to use the treatment off-label for patient benefit.

• Q: Enrollment in EC042 was slightly lower than originally planned. Is the trial still adequately powered to achieve statistical significance in the ITT population?

  A: Management explained the lower overall ITT enrollment came from a slightly different patient proportion than originally modeled, but the trial still met its target of 220 patients for the MITT (primary analysis) population, which is the key population for FDA review. Since the benefit of Selinexor is driven by P53 status rather than MMR status, the trial remains well-powered to show statistically significant benefit in both the MITT and ITT populations.

• Q: How much incremental commercial organization expansion will be needed if both indications are approved, and what is the status of supply preparedness?

  A: Management noted most pre-launch work is already completed, with existing teams already conducting KOL engagement, messaging development, and account mapping. The company has an established U.S. manufacturing and supply chain ready to support uptake. There will be a small incremental increase in sales coverage for gynecologic oncologists, but the treating physician population for both new indications is highly concentrated, so the team will be able to launch rapidly with limited additional spend.