Karyopharm Reports Third Quarter 2024 Financial Results and Highlights Recent Company Progress
– Achieves Third Quarter 2024 Total Revenue of
– Following FDA Alignment, Absolute Change in Total Symptom Score (Abs-TSS) Will Replace TSS50 as a Co-Primary Endpoint in Phase 3 SENTRY Trial in JAKi Naïve Myelofibrosis (MF); Expected Top-line Data Read-out Remains on Track for 2H 2025 –
– Narrows Full-Year 2024
"This quarter, we delivered our third consecutive quarter of
"A significant unmet need in myelofibrosis remains, as less than half of patients achieve SVR35 with each of the approved JAKi inhibitors. I am encouraged by the Phase 1 trial which evaluated the combination of selinexor and ruxolitinib, as it shows an approximate doubling of SVR35 to 80% compared to historical JAKi monotherapy and a meaningful 18.5 point improvement in Abs-TSS at week 24 compared to baseline," said Dr.
Third Quarter 2024 and Recent Highlights
XPOVIO Commercial Performance
- Achieved
U.S. net product revenue of$29.5 million for the third quarter of 2024, compared to$28.0 million for the second quarter of 2024 and$30.2 million for the third quarter of 2023. - XPOVIO net product revenue was supported by quarter-over-quarter double digit growth in demand, partially offset by higher gross-to-net quarter-over-quarter largely due to higher proportion of 340B book of business.
- Continued quarter-over-quarter demand growth with strong demand growth in the community setting, which represents approximately 60% of overall net product revenues. In the academic setting, demand for XPOVIO grew quarter-over-quarter amidst ongoing competitive pressures with continued use of XPOVIO preceding and following T-cell therapies in later lines.
- Expanded global patient access for selinexor in the third quarter of 2024 with favorable reimbursement decisions in
France andItaly and additional regulatory approvals in Turkiye,South Korea ,Thailand andMalaysia .
Research and Development (R&D) Highlights
Myelofibrosis
- Following recent alignment with the FDA, absolute change in total symptom score (Abs-TSS) at Week 24 will replace total symptom improvement of ≥ 50% (TSS50) as a co-primary endpoint in the pivotal Phase 3 SENTRY trial of selinexor in combination with ruxolitinib in JAKi naive myelofibrosis. Abs-TSS measures the average improvement in patient symptom scores over 24 weeks relative to the patient's baseline symptom score and is an accepted measure that has been used in other Phase 3 clinical trials in myelofibrosis to evaluate the benefit/risk of an add-on treatment, such as selinexor, to the current standard of care. Spleen volume reduction ≥35% (SVR35) at Week 24 will remain as a co-primary endpoint. These two co-primary endpoints will be tested sequentially starting with SVR35 followed by Abs-TSS.
- Proactively increasing the total sample size of the SENTRY trial to approximately 350 patients to further increase the statistical powering. The trial continues to enroll patients with strong momentum with expected top-line data read-out remaining in the second half of 2025.
- SENTRY-2 Phase 2 trial of selinexor monotherapy in JAKi naïve patients with moderate thrombocytopenia continues to enroll patients. The Company expects to present preliminary data from this trial in late 2024 or early 2025.
Endometrial Cancer
- Long-term follow-up data from a pre-specified exploratory subgroup analysis of patients with advanced or recurrent TP53 wild-type endometrial cancer from the SIENDO study (NCT03555422) were presented with expanded exploratory quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) for the proficient mismatched repair status (pMMR) TP53 wild-type subgroup at the
International Gynecological Cancer Society (IGCS) conference inOctober 2024 . These data showed the restricted mean Q-TWiST for selinexor to be 30 months compared to 17 months for placebo, resulting in a difference of 13 months. - Pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer continues to enroll patients and is expected to read-out top-line data in early 2026.
Multiple Myeloma
- Pivotal XPORT-MM-031 (EMN29) Phase 3 trial, in collaboration with the European Myeloma Network, evaluating an oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd) in patients with previously treated multiple myeloma now has a targeted enrollment of approximately 120 patients which leverages the positively evolving data observed with SPd 40 mg. Pending regulatory agency feedback on the updated protocol, the Company will provide guidance on the top-line data readout timeline from this trial.
2024 Financial Outlook
Based on its current operating plans, Karyopharm has further narrowed its guidance for full year 2024 as follows:
- Total revenue to be in the range of
$145.0 million to$155.0 million as compared to the Company's prior guidance of$145.0 million to$160.0 million . Total revenue consists ofU.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners. -
U.S. XPOVIO net product revenue to be in the range of$110.0 million to$115.0 million as compared to the Company's prior guidance of$105.0 million to$120.0 million . - R&D and selling, general and administrative (SG&A) expenses to be in the range of
$255.0 million to$265.0 million , which includes approximately$20.0 million estimated non-cash stock-based compensation expense, as compared to the Company's prior guidance of$250.0 million to$265.0 million . - The Company expects that its existing cash, cash equivalents and investments, the revenue it expects to generate from XPOVIO net product sales and its license agreements and ongoing disciplined expense management and cost saving measures, will be sufficient to fund its planned operations into the first quarter of 2026.1
1Excluding re-payment of
Third Quarter 2024 Financial Results
Total revenue: Total revenue for the third quarter of 2024 was
Net product revenue: Net product revenue for the third quarter of 2024 was
License and other revenue: License and other revenue for the third quarter of 2024 was
Cost of sales: Cost of sales for the third quarter of 2024 was
R&D expenses: R&D expenses for the third quarter of 2024 were
SG&A expenses: SG&A expenses for the third quarter of 2024 were
Interest income: Interest income for the third quarter of 2024 was
Interest expense: Interest expense for the third quarter of 2024 was
Other income: Other income for the third quarter of 2024 was
Net loss: Karyopharm reported a net loss of
Cash position: Cash, cash equivalents, restricted cash and investments as of
Conference Call Information
Karyopharm will host a conference call today,
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the
For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: medicalinformation@karyopharm.com
XPOVIO® (selinexor) is a prescription medicine approved:
- In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
- In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
- For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
- Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
- Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
- Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
- Serious Infection: Monitor for infection and treat promptly.
- Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
- Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
- Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions
- The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the
BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. - The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
- The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
To report SUSPECTED ADVERSE REACTIONS, contact
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's guidance on its 2024 total revenue, 2024 U.S. net product revenue and 2024 R&D and SG&A expenses; Karyopharm's expected cash runway; expectations with respect to commercialization efforts; the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma, and other diseases; and expectations with respect to the clinical development plans and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the
XPOVIO® and NEXPOVIO® are registered trademarks of
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited); (in thousands, except per share amounts) |
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Three Months Ended |
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Nine Months Ended |
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2024 |
|
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2023 |
|
|
2024 |
|
|
2023 |
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Revenues: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Product revenue, net |
|
$ |
29,516 |
|
|
$ |
30,207 |
|
|
$ |
83,554 |
|
|
$ |
86,955 |
|
License and other revenue |
|
|
9,267 |
|
|
|
5,802 |
|
|
|
31,141 |
|
|
|
25,331 |
|
Total revenue |
|
|
38,783 |
|
|
|
36,009 |
|
|
|
114,695 |
|
|
|
112,286 |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Cost of sales |
|
|
1,300 |
|
|
|
911 |
|
|
|
4,676 |
|
|
|
3,456 |
|
Research and development |
|
|
36,134 |
|
|
|
35,553 |
|
|
|
109,930 |
|
|
|
99,369 |
|
Selling, general and administrative |
|
|
27,632 |
|
|
|
30,805 |
|
|
|
88,251 |
|
|
|
101,193 |
|
Total operating expenses |
|
|
65,066 |
|
|
|
67,269 |
|
|
|
202,857 |
|
|
|
204,018 |
|
Loss from operations |
|
|
(26,283) |
|
|
|
(31,260) |
|
|
|
(88,162) |
|
|
|
(91,732) |
|
Other income (expense): |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Interest income |
|
|
1,832 |
|
|
|
2,750 |
|
|
|
5,918 |
|
|
|
8,423 |
|
Interest expense |
|
|
(11,385) |
|
|
|
(6,073) |
|
|
|
(26,218) |
|
|
|
(17,615) |
|
Gain on extinguishment of debt |
|
|
— |
|
|
|
— |
|
|
|
44,702 |
|
|
|
— |
|
Other income (expense), net |
|
|
3,792 |
|
|
|
89 |
|
|
|
18,284 |
|
|
|
(145) |
|
Total other income (expense), net |
|
|
(5,761) |
|
|
|
(3,234) |
|
|
|
42,686 |
|
|
|
(9,337) |
|
Loss before income taxes |
|
|
(32,044) |
|
|
|
(34,494) |
|
|
|
(45,476) |
|
|
|
(101,069) |
|
Income tax provision |
|
|
(28) |
|
|
|
(12) |
|
|
|
(166) |
|
|
|
(193) |
|
Net loss |
|
$ |
(32,072) |
|
|
$ |
(34,506) |
|
|
$ |
(45,642) |
|
|
$ |
(101,262) |
|
Basic net loss per share |
|
$ |
(0.26) |
|
|
$ |
(0.30) |
|
|
$ |
(0.38) |
|
|
$ |
(0.89) |
|
Diluted net loss per share |
|
$ |
(0.26) |
|
|
$ |
(0.30) |
|
|
$ |
(0.69) |
|
|
$ |
(0.89) |
|
Weighted-average number of common shares |
|
|
125,010 |
|
|
|
114,401 |
|
|
|
120,513 |
|
|
|
114,033 |
|
Weighted-average number of common shares |
|
|
125,010 |
|
|
|
114,401 |
|
|
|
126,606 |
|
|
|
114,033 |
|
CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited); (in thousands) |
|
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|
||||||
|
|
|
|
|
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Assets |
|
|
|
|
|
||
Cash, cash equivalents and investments |
$ |
133,526 |
|
|
$ |
191,443 |
|
Restricted cash |
|
339 |
|
|
|
961 |
|
Accounts receivable |
|
31,778 |
|
|
|
26,962 |
|
Other assets |
|
23,833 |
|
|
|
21,072 |
|
Total assets |
$ |
189,476 |
|
|
$ |
240,438 |
|
Liabilities and stockholders' deficit |
|
|
|
|
|
||
Convertible senior notes due 2025 |
$ |
24,392 |
|
|
$ |
170,919 |
|
Convertible senior notes due 2029 |
|
72,091 |
|
|
|
— |
|
Senior secured term loan |
|
94,109 |
|
|
|
— |
|
Deferred royalty obligation |
|
73,499 |
|
|
|
132,479 |
|
Other liabilities |
|
85,032 |
|
|
|
73,246 |
|
Total liabilities |
|
349,123 |
|
|
|
376,644 |
|
Total stockholders' deficit |
|
(159,647) |
|
|
|
(136,206) |
|
Total liabilities and stockholders' deficit; 125,303 and 114,915 shares issued and |
$ |
189,476 |
|
|
$ |
240,438 |
|
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