- Additional reimbursements of XPOVIO® in APAC markets are expected. MM, the second most common hematologic malignancy, is caused by the dysregulated proliferation of plasma cells. Patients with MM face a range of challenges including a high relapse rate, short survival, and limited treatment options. According to market data, the global MM market has exceeded US$17 billion in 2023 and is expected to reach US$ 26 billion by 2028, with a compound annual growth rate (CAGR) of 8.7%[1]. Antengene has already su ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-36167 Karyopharm Therapeutics Inc. (Exact name of registrant as specified in its charter) (State or other jur ...

Revenue Performance - Total revenue for Q1 2024 was $33.1 million, a decrease from $38.7 million in Q1 2023[8] - U.S. net product revenue for XPOVIO® (selinexor) was $26.0 million, compared to $28.3 million in Q1 2023[11] - The company reaffirms full year 2024 total revenue guidance of $140.0 million to $160.0 million, including U.S. XPOVIO net product revenue guidance of $100.0 million to $120.0 million[18] - Total revenue for Q1 2024 was $33.126 million, a decrease of 14.4% from $38.698 million in Q1 2023[36] - Product revenue, net for Q1 2024 was $26.006 million, down from $28.288 million in Q1 2023, reflecting a decline of 8.0%[36] Expenses - R&D expenses for Q1 2024 were $35.4 million, up from $32.3 million in Q1 2023, primarily due to higher clinical trial costs[14] - SG&A expenses for Q1 2024 decreased to $29.5 million from $35.9 million in Q1 2023, attributed to cost reduction initiatives[15] - Research and development expenses increased to $35.425 million in Q1 2024, compared to $32.339 million in Q1 2023, marking an increase of 9.5%[36] Net Loss - The company reported a net loss of $37.4 million, or $0.32 per share, compared to a net loss of $34.1 million, or $0.30 per share, in Q1 2023[16] - The net loss for Q1 2024 was $37.362 million, compared to a net loss of $34.126 million in Q1 2023, representing an increase in loss of 6.9%[36] Cash Position - Cash position as of March 31, 2024, was $149.3 million, down from $192.4 million as of December 31, 2023[17] - Cash, cash equivalents, and investments decreased to $148.578 million as of March 31, 2024, down from $191.443 million at the end of 2023[38] Liabilities - Total liabilities as of March 31, 2024, were $373.413 million, slightly down from $376.644 million at the end of 2023[38] Share Information - The company reported a weighted-average number of common shares outstanding of 115.454 million for Q1 2024, compared to 113.481 million for Q1 2023[36] Product Development and Strategy - Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. and marketed in three oncology indications, with ongoing efforts for further regulatory approvals[31] - The company is focused on expanding its pipeline targeting high unmet need cancers, including multiple myeloma and diffuse large B-cell lymphoma[31] - Karyopharm's management provided guidance for 2024 total revenue and expenses, indicating a strategic focus on commercialization efforts and potential regulatory submissions[31] Royalty Agreement - The company amended its royalty agreement with HealthCare Royalty, reducing the royalty rate from 12.5% to 7.0%[7] Market Performance - Approximately 60% of XPOVIO net product revenue came from the community setting, with growth in new patient starts despite increased competition[5] Future Expectations - The company expects to present preliminary results from the Phase 2 SENTRY-2 trial by the end of 2024[6]

– $148.0 Million (86%) of Existing Convertible Notes due in 2025 to be Exchanged for $111.0 Million of New Convertible Notes due in 2029 and Warrants – – Issues New $100.0 Million Senior Secured Term Loan due in 2028 – – Repays Principal Portion and Amends Royalty Agreement with HealthCare Royalty – NEWTON, Mass., May 8, 2024 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, announced today that it has entered into a ser ...

Thomas Barwick Topline Summary and Update Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a long-struggling commercial-stage biotech working on developing the market for their nuclear exportin 1 inhibitor selinexor. While it is currently approved to treat multiple myeloma in later lines of therapy, KPTI is on track to potentially expand the label into endometrial cancer, with a phase 3 trial eagerly anticipated (though still a ways away). Now that we know the abstracts being presented at the American Society ...

Financial Data and Key Metrics Changes - Total revenue for Q4 2023 was $33.7 million, consistent with Q4 2022, while total revenue for the full year 2023 was $146 million, down from $157.1 million in 2022 [55][56] - Net product revenue from US commercial sales of XPOVIO for Q4 2023 was $25.1 million, compared to $31.1 million in Q4 2022, and for the full year 2023, it was $112 million, down from $120.4 million in 2022 [56][60] - The gross-to-net discount for XPOVIO in Q4 2023 was 23.5%, and for the full year 2023, it was 22%, with expectations for 2024 to be in the 25% to 30% range [68] Business Line Data and Key Metrics Changes - XPOVIO's new patient share in the community setting approached 70% in the second to fourth line, representing double-digit growth year-over-year [44] - The community setting now accounts for two-thirds of the business, with a 20% year-over-year increase in prescribing sites [51][52] - The company expects US XPOVIO net product revenue for 2024 to be in the range of $100 million to $120 million, reflecting a balance of growth conviction and competitive market recognition [60][71] Market Data and Key Metrics Changes - The competitive landscape in the multiple myeloma market has intensified, particularly with the introduction of bispecific therapies in the second half of 2023, impacting demand in the academic setting [12][44] - Despite competition, the company achieved total demand growth year-on-year in the community setting in 2023, which is a key growth driver for 2024 [84] Company Strategy and Development Direction - The company is focused on advancing its late-stage pipeline, particularly in myelofibrosis and endometrial cancer, with three pivotal Phase 3 trials expected to read out results in 2025 [5][17] - The strategy includes shifting the use of selinexor into earlier lines of therapy, where patients tend to stay on treatment longer, thus increasing duration of therapy [95] - The company aims to leverage its existing commercial infrastructure to support rapid launches of selinexor in new indications, with a potential peak annual revenue of approximately $2 billion in the US alone [13][60] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing Phase 3 studies and the potential for selinexor to address high unmet needs in cancer treatment [67][73] - The company anticipates a cash runway into late 2025, supported by expected revenues from XPOVIO and partnerships [66][71] - Management highlighted the importance of evolving the regulatory landscape and potential changes in study design to enhance the value proposition of selinexor [105] Other Important Information - The company reported a decrease in R&D expenses due to reduced personnel costs, while SG&A expenses also decreased, reflecting cost optimization efforts [64][69] - The existing cash and investments as of December 31, 2023, totaled $192.4 million, down from $279.7 million in 2022 [70] Q&A Session Summary Question: Can you quantify the community versus academic setting growth in 2023? - The company achieved total demand growth year-on-year in the community setting, with a 20% increase in prescriber base, which is a significant growth driver for 2024 [84][85] Question: What is the impact of BCMA therapies moving into 2024? - The introduction of bispecific therapies posed a significant competitive threat in the academic setting, but the community setting has not seen a major impact yet [78] Question: Can you comment on the enrollment experience of the Phase 3 SPD triplet study in multiple myeloma? - Enrollment is progressing well, with significant interest in the study both in the US and EU, and completion of enrollment is expected later this year [115] Question: What is the company's cash position and runway? - The company finished 2023 with $192 million in cash, with a projected cash runway into late 2025, considering expected revenues and expenditures [119]

Financial Performance & Guidance - Karyopharm reported XPOVIO Net Product Revenue of $112 million for FY 2023 and $25 million for Q4 2023[118] - The company anticipates U S XPOVIO Net Product Revenue between $100 million and $120 million in 2024[119] - Karyopharm expects its cash runway to be sufficient to fund planned operations into late 2025[122] - Total revenue was $33.7 million for 4Q 2023 and $146 million for FY 2023[138] Clinical Development Programs - Karyopharm is conducting a Phase 3 trial of selinexor + ruxolitinib in treatment-naïve myelofibrosis (MF)[18] - Preliminary analysis from the Phase 3 SIENDO trial showed encouraging overall survival in the TP53 wild-type exploratory subgroup[29] - The company is planning to report top-line results from the pivotal EC-042 Phase 3 trial in TP53 wildtype endometrial cancer in 1H 2025[141] - Karyopharm is also expecting to report top-line results from the Phase 3 trial of selinexor + ruxolitinib in treatment-naïve MF in 2H 2025[141] Market Opportunity - Karyopharm estimates a potential for ~$2 billion in annual peak U S revenues from selinexor across multiple myeloma, endometrial cancer, and myelofibrosis[16, 20] - Approximately 20,000 people in the U S live with myelofibrosis[25] - In the U S each year, approximately 16,000 patients are diagnosed with advanced and recurrent endometrial cancer[100]

Financial Performance - As of December 31, 2023, the company reported an accumulated deficit of $1.5 billion and net losses of $143.1 million for the year, compared to $165.3 million in 2022 and $124.1 million in 2021[574]. - Total revenue for 2023 was $146.0 million, which included $112.0 million from XPOVIO net product revenue and $34.0 million from license revenue[574]. - Net product revenue from U.S. commercial sales of XPOVIO decreased by 7% in 2023 compared to 2022, primarily due to the closure of myeloma foundations that support Medicare Part D patients[585]. - License and other revenue decreased by $2.6 million in 2023 compared to 2022, mainly due to a decline in milestone-related revenue and royalty revenue from Antengene, partially offset by increased revenue from Menarini[587]. - Interest income rose significantly by $8.58 million (364%) in 2023 compared to 2022, contributing to a total other expense net decrease of $9.5 million (42%)[595]. - Net cash used in operating activities decreased by $56.83 million (38%) in 2023 compared to 2022, primarily due to reduced expenses and milestone payments received[602]. - The company received $32.0 million in milestone and upfront payments in 2023, with additional potential payments tied to development goals and sales milestones[607]. Expenses and Cost Management - Total operating expenses decreased by $23.7 million (8%) in 2023 compared to 2022, with research and development expenses down by $9.9 million (7%) and selling, general and administrative expenses down by $13.5 million (9%)[589][593]. - Research and development expenses for 2023 were $138.75 million, a decrease from $148.66 million in 2022, primarily due to a reduction in personnel costs and stock-based compensation[591]. - Clinical trial costs increased by $9.2 million (16%) in 2023, driven by advancements in three pivotal Phase 3 trials[591][592]. - Selling, general and administrative expenses are expected to decrease slightly in 2024 due to cost optimization efforts[594]. - The company anticipates research and development expenses to increase slightly in 2024 as it continues to advance its pivotal Phase 3 trials[592]. Cash and Liquidity - As of December 31, 2023, the company had $191.4 million in cash, cash equivalents, and investments[574]. - As of December 31, 2023, the company had cash, cash equivalents, and investments totaling $191.4 million, which are expected to fund operations for at least twelve months[619]. - The company has provided a security deposit of $0.3 million for its operating lease, classified as long-term restricted cash[612]. - The company does not believe its cash and investments have significant risk of default or illiquidity, but acknowledges potential instability in financial institutions[620]. Clinical Development and Commercialization - The company plans to continue clinical trials and seek additional approvals for selinexor in multiple high unmet need cancer indications, including endometrial cancer and multiple myeloma[573]. - The commercialization of XPOVIO is supported by a comprehensive patient and healthcare provider support program, KaryForward™, and a dedicated network of specialty pharmacy providers[571]. - The company announced in January 2024 that further clinical development of the eltanexor program is on hold to focus resources on prioritized late-stage programs[573]. - XPOVIO has received regulatory approval in over 40 countries outside the U.S. and is commercially available in a growing number of countries[572]. - The company expects changes in Medicare Part D under the Inflation Reduction Act to reduce the need for patient assistance programs in 2024 compared to 2023[586]. - License and other revenue is expected to increase in 2024 compared to 2023 due to anticipated milestone achievements[588]. - The company expects to continue incurring costs related to commercialization expenses for its products, depending on the responsibilities of collaborators[615]. Market and Risk Factors - The company is exposed to market risks related to interest rates, with an immediate 100 basis point shift in rates not expected to materially affect the fair market value of its investment portfolio[619]. - The company does not currently hedge its foreign currency exchange rate risk, which could impact costs related to contracts with organizations in Canada, the UK, and Europe[621]. - The company is subject to fluctuations in foreign currency rates for clinical trial budgets frequently denominated in foreign currencies[621]. - The company has incurred significant losses since inception and may not achieve profitability for several years, necessitating reliance on additional financing[616].

Financial Data and Key Metrics Changes - Total revenue for Q3 2023 was $36 million, slightly down from $36.1 million in Q3 2022 [36] - Net product revenue from U.S. sales of XPOVIO was $30.2 million in Q3 2023, compared to $32 million in Q3 2022, impacted by higher patient assistance program utilization and increased gross to net discounts [37] - Cash and cash equivalents totaled $209.2 million as of September 30, 2023, down from $279.7 million at the end of 2022, with a cash runway expected through late 2025 [39][40] Business Line Data and Key Metrics Changes - XPOVIO delivered $30.2 million in net sales in Q3 2023, with total demand year-over-year declining 3% compared to Q3 2022, primarily due to increased competition in late lines [17][32] - The utilization of the patient assistance program (PAP) contributed to 9% of total demand in Q3 2023, up from 4% in Q3 2022, reflecting higher patient engagement [18] - The NCCN has updated guidelines to recommend switching classes of therapy, enhancing XPOVIO's positioning in the treatment landscape [20] Market Data and Key Metrics Changes - The company expects total revenues in 2023 to be between $145 million and $160 million, with XPOVIO net U.S. product revenue projected between $110 million and $125 million [40] - The new patient share mix for XPOVIO in the second to fourth line was over 60%, representing approximately 20% growth year-over-year [49] Company Strategy and Development Direction - The company is focused on advancing its mid and late-stage pipeline, with three pivotal Phase 3 trials expected to read out data through 2024 and 2025 [4][90] - There is a strong emphasis on cost management, with a 12% reduction in R&D and SG&A expenses year-over-year for the first nine months of 2023 [38] - The company aims to leverage its commercialization capabilities and relationships in the community to drive growth across multiple indications [52] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for selinexor to change treatment paradigms in multiple myeloma and endometrial cancer [42][90] - The company is optimistic about the upcoming data readouts and the impact of recent guideline updates on XPOVIO's market positioning [60][76] Other Important Information - The company has reduced its workforce by approximately 20% to strengthen its financial position for ongoing Phase 3 studies [36] - The collaboration with BMS to evaluate selinexor in combination with mezigdomide is expected to enhance treatment options for multiple myeloma patients [93] Q&A Session Summary Question: Contextualizing new IMF data and Phase 3 top line data expectations - Management highlighted the impressive efficacy of the combination of selinexor and ruxolitinib in JAK naive patients, with a focus on the durability of responses [46] Question: Update on eltanexor development plans - Management remains enthusiastic about eltanexor's data in hard-to-treat patient populations, with encouraging survival rates observed [47] Question: Enrollment progress and repo rates in early line patients - Enrollment is proceeding well, driven by enthusiasm around new data, with a noted increase in new patient starts in earlier lines [57] Question: Impact of NCCN guideline updates on XPOVIO - The elevation of XPOVIO to category one in NCCN guidelines is expected to strengthen its position in the community and drive steady growth [60] Question: Overall survival data from the SIENDO Phase 3 study - Initial overall survival data is anticipated to be presented later this year, with ongoing monitoring of patient populations [71] Question: Impact of foundation closures on PAP - The impact of PAP is expected to remain similar in Q4 as in Q3, with anticipated changes in Medicare Part D design expected to reduce reliance on PAP in 2024 [85]

[PART I - FINANCIAL INFORMATION](index=3&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) Karyopharm Therapeutics Inc.'s unaudited condensed consolidated financial statements for Q3 and nine months ended September 30, 2023, are presented [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet shows a decrease in total assets from $358.2 million at the end of 2022 to $270.0 million as of September 30, 2023, primarily driven by a reduction in cash and cash equivalents Condensed Consolidated Balance Sheets (in thousands) | | September 30, 2023 | December 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $43,655 | $135,188 | | Investments | $164,660 | $142,779 | | Total current assets | $263,222 | $350,162 | | **Total assets** | **$269,960** | **$358,172** | | **Liabilities and Stockholders' Deficit** | | | | Total current liabilities | $62,079 | $65,908 | | Convertible senior notes | $170,702 | $170,105 | | **Total liabilities** | **$370,356** | **$374,828** | | **Total stockholders' deficit** | **($100,396)** | **($16,656)** | | **Total liabilities and stockholders' deficit** | **$269,960** | **$358,172** | [Condensed Consolidated Statements of Operations](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Total revenue for Q3 2023 was $36.0 million, with a net loss of $34.5 million, while nine-month revenue decreased to $112.3 million with a narrowed net loss of $101.3 million Condensed Consolidated Statements of Operations (in thousands, except per share amounts) | | For the Three Months Ended Sep 30, 2023 | For the Three Months Ended Sep 30, 2022 | For the Nine Months Ended Sep 30, 2023 | For the Nine Months Ended Sep 30, 2022 | | :--- | :--- | :--- | :--- | :--- | | Product revenue, net | $30,207 | $32,009 | $86,955 | $89,319 | | License and other revenue | $5,802 | $4,136 | $25,331 | $34,175 | | **Total revenue** | **$36,009** | **$36,145** | **$112,286** | **$123,494** | | Research and development | $35,553 | $31,359 | $99,369 | $117,730 | | Selling, general and administrative | $30,805 | $34,645 | $101,193 | $110,752 | | **Total operating expenses** | **$67,269** | **$66,984** | **$204,018** | **$231,827** | | Loss from operations | ($31,260) | ($30,839) | ($91,732) | ($108,333) | | **Net loss** | **($34,506)** | **($36,324)** | **($101,262)** | **($126,785)** | | **Net loss per share—basic and diluted** | **($0.30)** | **($0.45)** | **($0.89)** | **($1.60)** | [Condensed Consolidated Statements of Cash Flows](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities significantly decreased for the nine months ended September 30, 2023, while cash, cash equivalents, and restricted cash ended lower Condensed Consolidated Statements of Cash Flows (in thousands) | | For the Nine Months Ended September 30, 2023 | For the Nine Months Ended September 30, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | ($74,138) | ($122,711) | | Net cash used in investing activities | ($18,903) | ($38,958) | | Net cash provided by financing activities | $860 | $37,895 | | **Net decrease in cash, cash equivalents and restricted cash** | **($92,304)** | **($124,388)** | | Cash, cash equivalents and restricted cash at end of period | $44,581 | $73,057 | [Notes to Condensed Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes detail Karyopharm's business, key accounting policies, and breakdowns of revenues, inventory, financial instruments, investments, stock-based compensation, equity, and long-term obligations - The company's lead asset, XPOVIO® (selinexor), is approved for multiple myeloma and diffuse large B-cell lymphoma (DLBCL) in the U.S. and is commercialized by partners in approximately 40 countries outside the U.S.[22](index=22&type=chunk)[23](index=23&type=chunk) Product Revenue, Net (in thousands) | | For the Three Months Ended Sep 30, | For the Nine Months Ended Sep 30, | | :--- | :--- | :--- | | | 2023 | 2022 | 2023 | 2022 | | Gross product revenue | $37,981 | $39,178 | $111,387 | $108,947 | | Provisions for product revenue | ($7,774) | ($7,169) | ($24,432) | ($19,628) | | **Total product revenue, net** | **$30,207** | **$32,009** | **$86,955** | **$89,319** | License and Other Revenue (in thousands) | | For the Three Months Ended Sep 30, | For the Nine Months Ended Sep 30, | | :--- | :--- | :--- | | | 2023 | 2022 | 2023 | 2022 | | Menarini | $5,564 | $1,618 | $19,912 | $15,235 | | Antengene | $80 | $1,532 | $1,952 | $11,533 | | Other | $158 | $986 | $3,467 | $7,407 | | **Total license and other revenue** | **$5,802** | **$4,136** | **$25,331** | **$34,175** | - The company has **$172.5 million** in principal of 3.00% convertible senior notes due 2025. As of September 30, 2023, the conditions for conversion had not been met.[60](index=60&type=chunk)[62](index=62&type=chunk)[64](index=64&type=chunk) - A deferred royalty obligation exists with HealthCare Royalty Partners (HCR), where Karyopharm received **$135.0 million** in total investment and makes tiered percentage payments on net revenues of selinexor. Total payments are capped at **195%** of the investment amount.[67](index=67&type=chunk)[68](index=68&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations (MD&A)](index=18&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations%20(MD%26A)) Management discusses the company's financial condition, results of operations, and liquidity, highlighting XPOVIO® commercialization and pipeline development [Results of Operations](index=19&type=section&id=Results%20of%20Operations) Q3 2023 total revenue was flat, with net product revenue impacted by patient assistance programs, while R&D expenses rose and SG&A expenses fell, leading to a narrowed net loss Comparison of Operations (in thousands) | | For the Three Months Ended Sep 30, 2023 | For the Three Months Ended Sep 30, 2022 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Product revenue, net | $30,207 | $32,009 | ($1,802) | (6)% | | License and other revenue | $5,802 | $4,136 | $1,666 | 40% | | **Total revenue** | **$36,009** | **$36,145** | **($136)** | **(0)%** | | Research and development | $35,553 | $31,359 | $4,194 | 13% | | Selling, general and administrative | $30,805 | $34,645 | ($3,840) | (11)% | | **Net loss** | **($34,506)** | **($36,324)** | **$1,818** | **(5)%** | - Net product revenue in 2023 was adversely impacted by approximately **$1.2 million** in Q3 and **$5.4 million** year-to-date due to providing XPOVIO at no charge through its Patient Assistance Program (PAP) following the closure of several myeloma foundation support programs.[88](index=88&type=chunk) - The decrease in nine-month license and other revenue was primarily due to the recognition of **$7.8 million** of milestone-related revenue from Antengene in 2022 which did not recur in 2023.[90](index=90&type=chunk) - The increase in Q3 R&D expenses was driven by a **$7.1 million** rise in clinical trial costs for three pivotal Phase 3 studies, partially offset by lower personnel and stock-based compensation costs due to reduced headcount.[95](index=95&type=chunk) [Liquidity and Capital Resources](index=22&type=section&id=Liquidity%20and%20Capital%20Resources) As of September 30, 2023, Karyopharm had $208.3 million in liquidity, expected to fund operations for at least twelve months, with decreased cash used in operating activities - As of September 30, 2023, the company's principal source of liquidity was **$208.3 million** of cash, cash equivalents and investments.[104](index=104&type=chunk) - Management believes that existing cash, cash equivalents and investments will be sufficient to fund current operating plans and capital expenditure requirements for at least **twelve months** from the report's issuance date.[104](index=104&type=chunk) Cash Flow Summary (in thousands) | | For the Nine Months Ended Sep 30, 2023 | For the Nine Months Ended Sep 30, 2022 | $ Change | | :--- | :--- | :--- | :--- | | Net cash used in operating activities | ($74,138) | ($122,711) | $48,573 | | Net cash used in investing activities | ($18,903) | ($38,958) | $20,055 | | Net cash provided by financing activities | $860 | $37,895 | ($37,035) | - The company has a 2023 Open Market Sale Agreement with Jefferies to sell up to **$100.0 million** of common stock. No shares were sold under this agreement during the nine months ended September 30, 2023.[111](index=111&type=chunk)[112](index=112&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=25&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risks are U.S. interest rates and foreign currency exchange rates, with interest rate risk considered low due to short-term investments - The primary market risk is interest rate sensitivity on its **$208.3 million** portfolio of cash, cash equivalents, and investments. An immediate **100 basis point** shift in interest rates is not expected to have a material effect.[121](index=121&type=chunk) - The company is exposed to foreign currency exchange rate risk through contracts with CROs and CMOs in Canada and Europe. It does not currently hedge this risk.[123](index=123&type=chunk) [Item 4. Controls and Procedures](index=25&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of September 30, 2023, with no material changes in internal control over financial reporting - Based on an evaluation as of September 30, 2023, the President and CEO and the Executive VP and CFO concluded that the company's disclosure controls and procedures were effective at the reasonable assurance level.[124](index=124&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended September 30, 2023, that have materially affected, or are reasonably likely to materially affect, internal controls.[125](index=125&type=chunk) [PART II - OTHER INFORMATION](index=26&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) [Item 1A. Risk Factors](index=26&type=section&id=Item%201A.%20Risk%20Factors) This section details material risks and uncertainties that could adversely affect the company's business, financial condition, and results of operations [Risks Related to Commercialization and Product Development](index=26&type=section&id=Risks%20Related%20to%20Commercialization%20and%20Product%20Development) The company's success depends on XPOVIO's commercial success, facing intense competition, and risks from long, expensive, and uncertain clinical development processes - The business is substantially dependent on the commercial success of XPOVIO. Failure to successfully commercialize it will materially harm the business.[130](index=130&type=chunk) - The company faces substantial competition from major pharmaceutical and biotech companies, with several new novel therapeutics recently entering the multiple myeloma market, such as TECVAYLI™, ELREXFIO™, and TALVEY™.[134](index=134&type=chunk) - Serious adverse side effects related to XPOVIO, such as fatigue, nausea, and cytopenias, could delay or prevent regulatory approval, limit commercial value, or lead to significant negative financial consequences.[144](index=144&type=chunk)[145](index=145&type=chunk) [Risks Related to Regulatory Matters](index=35&type=section&id=Risks%20Related%20to%20Regulatory%20Matters) The company faces risks from expensive, uncertain regulatory approvals, post-marketing requirements, healthcare reform, and stringent data privacy laws - The regulatory approval process is expensive, time-consuming, and uncertain, and the company may not receive approvals for commercialization in a timely manner, or at all.[172](index=172&type=chunk) - XPOVIO's approval for DLBCL is under the FDA's Accelerated Approval Program, which requires a post-marketing confirmatory trial. Failure to verify clinical benefit in this trial could lead the FDA to withdraw its approval for this indication.[188](index=188&type=chunk) - The Inflation Reduction Act (IRA) of 2022 has significant implications, including authorizing Medicare to negotiate drug prices (starting 2026) and imposing rebates for price increases that outpace inflation, which could adversely affect revenue.[223](index=223&type=chunk)[224](index=224&type=chunk) - The company is subject to stringent data privacy laws like GDPR in Europe and CCPA/CPRA in California, which regulate the processing of personal data. Non-compliance can lead to significant fines and reputational harm.[242](index=242&type=chunk)[246](index=246&type=chunk)[248](index=248&type=chunk) [Risks Related to Our Financial Position and Capital Requirements](index=52&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Capital%20Requirements) The company has a history of significant losses, requires additional funding, and its indebtedness contains covenants that could restrict operations - The company has incurred significant losses since inception, with an accumulated deficit of **$1.4 billion** as of September 30, 2023, and expects to continue incurring losses.[270](index=270&type=chunk) - Additional funding will be needed to achieve business objectives. If unable to raise capital when needed, the company may be forced to delay, reduce, or eliminate R&D programs or commercialization efforts.[275](index=275&type=chunk) - The Revenue Interest Agreement with HCR contains covenants that, if violated, could lead to accelerated payments or foreclosure on all present and future assets related to selinexor.[278](index=278&type=chunk) [Risks Related to Our Dependence on Third Parties](index=57&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) The company heavily relies on third parties for international collaborations, U.S. product distribution, clinical trials, and manufacturing, posing significant operational risks - The company depends on collaborations with third parties (e.g., Antengene, Menarini) for development, marketing, and commercialization of its products outside the U.S. Unsuccessful collaborations could force the company to alter its plans.[289](index=289&type=chunk)[290](index=290&type=chunk) - The company relies on a limited number of specialty pharmacies and distributors for U.S. sales of XPOVIO. Any failure by these parties to perform could adversely affect results.[295](index=295&type=chunk) - The company is completely dependent on third-party contract manufacturers, including a single source supplier for its active pharmaceutical ingredient. Any disruption could delay clinical development, marketing approval, or commercialization.[305](index=305&type=chunk)[308](index=308&type=chunk) [Risks Related to Our Intellectual Property](index=61&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) Success depends on obtaining and maintaining patent protection, facing litigation risks, and potential competition from generic versions of approved products - The company's success depends on its ability to obtain and maintain patent protection. The patent position of biotech companies is highly uncertain, and pending applications may not result in issued patents that provide meaningful protection.[310](index=310&type=chunk)[312](index=312&type=chunk) - The company may become involved in expensive and time-consuming lawsuits to protect its patents or defend against infringement claims by third parties, the outcomes of which are uncertain.[318](index=318&type=chunk)[319](index=319&type=chunk) - Upon regulatory approval of its products, competitors could enter the market with generic versions by filing ANDAs or 505(b)(2) applications, which may lead to a material decline in sales of the company's products.[324](index=324&type=chunk) [Risks Related to Our Operations and Employee Matters](index=65&type=section&id=Risks%20Related%20to%20Our%20Operations%20and%20Employee%20Matters) Future success relies on retaining key personnel and is vulnerable to increasing cyber incidents that could disrupt operations and lead to data loss - The company is highly dependent on its key management and scientific teams and faces significant competition in recruiting and retaining qualified personnel.[335](index=335&type=chunk)[336](index=336&type=chunk) - Internal computer systems are vulnerable to cyber incidents such as malware, ransomware, and phishing. A security breach could result in a material disruption of development programs, loss of trade secrets, and significant liability.[337](index=337&type=chunk)[339](index=339&type=chunk) [Risks Related to Our Common Stock](index=66&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) The common stock price may be volatile, facing delisting risks from Nasdaq non-compliance, and corporate provisions could deter potential acquisitions - Failure to comply with Nasdaq's continued listing requirements, such as the minimum **$1.00** bid price, could lead to delisting, which would negatively impact the stock's price and liquidity. The stock price has recently closed below **$1.00** per share.[341](index=341&type=chunk) - The stock price has been and may continue to be volatile, influenced by factors such as clinical trial results, competitor announcements, regulatory developments, and general market conditions.[345](index=345&type=chunk) - Provisions in the corporate charter and Delaware law, such as a classified board and inability of stockholders to act by written consent, could discourage or delay a potential acquisition.[342](index=342&type=chunk)[344](index=344&type=chunk) [Item 5. Other Information](index=71&type=section&id=Item%205.%20Other%20Information) This section discloses information regarding director and officer trading arrangements under Rule 10b5-1, with no adoptions or terminations in Q3 2023 - During the third quarter of 2023, none of the company's directors or officers adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement.[365](index=365&type=chunk) [Item 6. Exhibits](index=72&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including a common stock purchase warrant, an amendment to the Revenue Interest Financing Agreement, and certifications - Lists exhibits filed with the report, including a Common Stock Purchase Warrant, the Second Amendment to the Revenue Interest Financing Agreement, and CEO/CFO certifications pursuant to the Sarbanes-Oxley Act.[367](index=367&type=chunk) [Signatures](index=73&type=section&id=Signatures) The report is duly signed and authorized by the company's Principal Executive Officer and Principal Financial and Accounting Officer on November 2, 2023 - The report was signed on November 2, 2023, by Richard Paulson, President and Chief Executive Officer, and Michael Mason, Executive Vice President, Chief Financial Officer and Treasurer.[372](index=372&type=chunk)