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)

Second Quarter 2023 Financial Results & Business Update On Today's Call Elhan Webb, CFA, Senior Vice President, Investor Relations Richard Paulson, President and Chief Executive Officer • Commercial Highlights • Closing Remarks Richard Paulson, President and Chief Executive Officer This presentation 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 2023 total rev ...

Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q2 2023 Earnings Conference Call August 2, 2023 8:00 AM ET Company Participants Elhan Webb - Senior Vice President, Investor Relations Richard Paulson - President and Chief Executive Officer Reshma Rangwala - Chief Medical Officer Sohanya Cheng - Chief Commercial Officer Michael Mason - Chief Financial Officer Conference Call Participants Kevin Strang - Jefferies Colleen Kusy - Baird Nicole Gabreski - Piper Sandler Brian Abrams - RBC Capital Markets Operator Good m ...

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 June 30, 2023 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) Delaware 26-3931704 ...

Karyopharm Therapeutics, Inc. (NASDAQ:KPTI) Q1 2023 Earnings Conference Call May 4, 2023 8:00 AM ET Company Participants Elhan Webb - SVP, IR Richard Paulson - President, CEO & Director Sohanya Cheng - EVP & Chief Commercial Officer Reshma Rangwala - Chief Medical Officer Michael Mason - EVP, CFO & Treasurer Conference Call Participants Peter Lawson - Barclays Kevin Strang - Jefferies Colleen Kusy - Robert W. Baird Nicole Gabreski - Piper Sandler Eric Joseph - JPMorgan Operator Good morning. My name is ...

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, 2023 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) Delaware 26-3931704 ...

PART I [Business](index=5&type=section&id=Item%201.%20Business) Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on pioneering novel cancer therapies by developing and commercializing first-in-class drugs targeting nuclear export [Overview](index=5&type=section&id=Overview) Karyopharm is a commercial-stage pharmaceutical company focused on developing and commercializing first-in-class XPO1 inhibitor drugs like XPOVIO for cancer treatment - Karyopharm is a commercial-stage pharmaceutical company focused on discovering, developing, and commercializing first-in-class drugs that inhibit the nuclear export protein XPO1 for treating cancer and other diseases[15](index=15&type=chunk) - The company's lead asset, XPOVIO® (selinexor), is the first oral XPO1 inhibitor to receive FDA approval and is marketed in the U.S. for multiple myeloma and diffuse large B-cell lymphoma (DLBCL)[15](index=15&type=chunk)[19](index=19&type=chunk) - XPOVIO/NEXPOVIO has received regulatory approval in various indications in approximately **40 countries** outside the U.S., with commercialization managed by partners[17](index=17&type=chunk) [Our Strategy](index=6&type=section&id=Our%20Strategy) The company's strategy focuses on maximizing XPOVIO's commercial value, advancing a prioritized clinical pipeline, maintaining strong leadership, and ensuring a well-capitalized business - The company's strategy is built on four key pillars[20](index=20&type=chunk) - **Maximize XPOVIO's Commercial Value:** Expand use in earlier-line multiple myeloma and globally through partners[23](index=23&type=chunk) - **Focus on Prioritized Clinical Pipeline:** Concentrate on four priority programs: multiple myeloma, endometrial cancer, myelofibrosis (MF), and myelodysplastic neoplasms (MDS)[23](index=23&type=chunk) - **Provide Strong Leadership:** Maintain a strong leadership team to achieve scientific, clinical, and commercial goals[23](index=23&type=chunk) - **Maintain a Well-capitalized Business:** Ensure sufficient capital to advance clinical development opportunities[23](index=23&type=chunk) [Our Programs to Treat Cancer](index=6&type=section&id=Our%20Programs%20to%20Treat%20Cancer) The company's core technology involves Selective Inhibitor of Nuclear Export (SINE) compounds, such as selinexor and eltanexor, which block the XPO1 protein, forcing tumor suppressor proteins to accumulate in the cell nucleus, counteracting oncogenic pathways - The company's SINE compounds, selinexor and eltanexor, are designed to inhibit the XPO1 protein, forcing the nuclear accumulation of tumor suppressor proteins and thereby counteracting cancer cell growth[26](index=26&type=chunk)[27](index=27&type=chunk) Key Clinical Trial Pipeline | Drug | Regimen | Indication | Study Name | Stage | | :--- | :--- | :--- | :--- | :--- | | **Selinexor** | w/dexamethasone | Multiple myeloma (penta-refractory) | STORM | Commercial | | | w/bortezomib + dexamethasone | Multiple myeloma (2L+) | BOSTON | Commercial | | | monotherapy | DLBCL (R/R) | SADAL | Commercial | | | w/R-GDP | DLBCL (R/R) | XPORT-DLBCL-030 | Late Stage | | | monotherapy | Endometrial cancer (maintenance; TP53 wild-type) | XPORT-EC-042 | Late Stage | | | w/pomalidomide + dexamethasone | Multiple myeloma (2L+) | XPORT-MM-031 | Late Stage | | | monotherapy | Myelofibrosis (previously treated) | XPORT-MF-035 | Mid Stage | | | w/ruxolitinib | Myelofibrosis (treatment naïve) | XPORT-MF-034 | Mid Stage | | **Eltanexor** | monotherapy | Myelodysplastic neoplasms (refractory) | KCP-8602-801 | Mid Stage | [Collaboration, License and Other Strategic Agreements](index=14&type=section&id=Collaboration%2C%20License%20and%20Other%20Strategic%20Agreements) Karyopharm maintains commercial rights in the U.S. and Japan while leveraging strategic partnerships for global reach, including agreements with Menarini, Antengene, FORUS, and Promedico - **Menarini:** Granted exclusive commercialization rights for selinexor in Europe, Latin America, and other territories. Karyopharm received a **$75.0 million upfront payment** in December 2021 and is eligible for up to **$202.5 million in milestones** plus tiered royalties[80](index=80&type=chunk)[81](index=81&type=chunk) - **Antengene:** Granted exclusive rights to develop and commercialize selinexor, eltanexor, and other compounds in China and other Asia-Pacific territories. Karyopharm has received upfront payments and recognized milestone revenue of **$7.8 million in 2022**, **$29.3 million in 2021**, and **$9.8 million in 2020**[82](index=82&type=chunk)[83](index=83&type=chunk) - **FORUS Therapeutics:** Exclusive distribution agreement for XPOVIO in Canada. Karyopharm received a **$5.0 million upfront payment in 2020** and is eligible for milestones and double-digit royalties[84](index=84&type=chunk) - **Promedico Ltd.:** Exclusive distribution agreement for XPOVIO in Israel and surrounding territories, with eligibility for milestone payments and double-digit royalties[85](index=85&type=chunk) [Intellectual Property](index=16&type=section&id=Intellectual%20Property) The company's intellectual property strategy relies on a combination of patents, trade secrets, and know-how, with selinexor and eltanexor patent portfolios extending to at least 2032 and 2034, respectively - As of February 10, 2023, the company owned **32 U.S. patents**, with **12 pending U.S. applications**, **112 granted foreign patents**, and **92 pending foreign applications**[89](index=89&type=chunk) - The selinexor patent portfolio covers composition of matter, methods of use, and manufacturing, with patents expected to expire no earlier than **2032**, not including potential extensions[91](index=91&type=chunk) - The eltanexor patent portfolio covers composition of matter and methods of making and using the compound, with patents expected to expire no earlier than **2034**, not including potential extensions[91](index=91&type=chunk) - The company relies on unpatented trade secrets and know-how, protected by confidentiality and invention assignment agreements with employees, collaborators, and consultants[96](index=96&type=chunk)[97](index=97&type=chunk) [Competition](index=18&type=section&id=Competition) Karyopharm faces intense competition from major pharmaceutical and biotechnology companies with greater financial and operational resources across its therapeutic areas, including multiple myeloma, endometrial cancer, myelofibrosis, and DLBCL - The company faces competition from major pharmaceutical and biotech companies with significantly greater financial resources and expertise in R&D, manufacturing, and marketing[101](index=101&type=chunk) - **Multiple Myeloma:** XPOVIO competes with IMiDs (e.g., lenalidomide), PIs (e.g., bortezomib), monoclonal antibodies (e.g., daratumumab), CAR-T therapies, and newly approved bispecific T-Cell engagers like TECVAYLI™[107](index=107&type=chunk) - **Endometrial Cancer:** Competes with chemotherapy, targeted drugs, and investigational therapies including checkpoint inhibitors and PARP inhibitors. There are currently no approved maintenance therapies[108](index=108&type=chunk) - **Myelofibrosis:** The standard of care is JAK inhibitors (e.g., ruxolitinib). Late-stage competition includes other JAKi and non-JAKi therapies[110](index=110&type=chunk)[111](index=111&type=chunk) - **DLBCL:** Competes with multi-agent chemotherapy, CAR-T therapies, antibody-drug conjugates (e.g., polatuzumab vedotin-piiq), and a CD19-directed antibody (tafasitamab-cxix)[113](index=113&type=chunk)[114](index=114&type=chunk) [Sales and Marketing](index=20&type=section&id=Sales%20and%20Marketing) In the U.S., Karyopharm commercializes XPOVIO with its own focused team of approximately 70 field-based employees and a patient support program, KaryForward®, while relying on partners for ex-U.S. commercialization - The company commercializes XPOVIO in the U.S. with a field-based team of approximately **70 employees** targeting healthcare professionals in academic and community settings[117](index=117&type=chunk) - The KaryForward® patient support program provides assistance with insurance coverage, co-pay support for eligible commercial patients, and a Patient Assistance Program for uninsured or underinsured patients[119](index=119&type=chunk) - The company intends to commercialize its products alone in the U.S. and rely on partners for development and commercialization in territories outside of the U.S[117](index=117&type=chunk) [Manufacturing](index=21&type=section&id=Manufacturing) Karyopharm outsources all manufacturing to third-party contract manufacturers, relying on a single source for its active pharmaceutical ingredient and drug product, while maintaining over two years of inventory to mitigate supply risks - The company outsources all manufacturing and relies on third-party contract manufacturers for clinical and commercial supplies[120](index=120&type=chunk) - Karyopharm currently relies on a single source supplier for its active pharmaceutical ingredient (API) and drug product manufacturing[121](index=121&type=chunk) - To minimize supply disruption risk, the company maintains inventory levels sufficient to exceed its **two-year forecasts** for XPOVIO[122](index=122&type=chunk) [Government Regulation](index=21&type=section&id=Government%20Regulation) The company's operations are subject to extensive regulation by the FDA and foreign authorities, covering all stages from R&D to post-market surveillance, including the U.S. drug approval process, healthcare reform, and data privacy laws - The company is subject to extensive regulation by the FDA in the U.S. and comparable authorities in foreign jurisdictions, covering all stages from research and development to post-market surveillance[124](index=124&type=chunk) - The U.S. drug approval process involves preclinical studies, submitting an Investigational New Drug (IND) application, and conducting human clinical trials (Phase 1, 2, 3) before submitting a New Drug Application (NDA)[126](index=126&type=chunk)[143](index=143&type=chunk) - The Inflation Reduction Act of 2022 (IRA) will impact the company through provisions allowing Medicare to negotiate drug prices (beginning in 2026), imposing rebates for price increases that outpace inflation, and capping Medicare out-of-pocket drug costs[221](index=221&type=chunk)[222](index=222&type=chunk) - The company is subject to stringent data privacy laws, including HIPAA in the U.S., the GDPR in Europe, and the CCPA/CPRA in California, which govern the use and protection of personal and health information[225](index=225&type=chunk)[226](index=226&type=chunk)[255](index=255&type=chunk) [Human Capital](index=43&type=section&id=Human%20Capital) As of February 10, 2023, Karyopharm had 385 employees and focuses on attracting, retaining, and developing its workforce through competitive compensation, comprehensive benefits, career development programs, and diversity and inclusion initiatives - As of February 10, 2023, the company had **385 employees**, with none represented by a labor union[266](index=266&type=chunk) - The company offers competitive total rewards, including equity grants to all new employees, an Employee Stock Purchase Plan, and a **4% match** for its 401(k) plan[261](index=261&type=chunk) - Karyopharm supports employee growth through a formal mentorship program, tuition assistance, and leadership training, and promotes diversity through various internal programs and external partnerships[263](index=263&type=chunk)[265](index=265&type=chunk) [Information about our Executive Officers](index=44&type=section&id=Information%20about%20our%20Executive%20Officers) This section provides a list of Karyopharm's executive officers as of February 10, 2023, detailing their names, ages, and positions within the company Executive Officers as of February 10, 2023 | Name | Age | Position | | :--- | :--- | :--- | | Richard Paulson, M.B.A | 55 | President and Chief Executive Officer | | Sohanya Cheng, M.B.A. | 40 | Executive Vice President, Chief Commercial Officer | | Michael Mano, J.D. | 46 | Senior Vice President, General Counsel and Secretary | | Michael Mason, C.P.A., M.B.A. | 48 | Executive Vice President, Chief Financial Officer and Treasurer | | Stephen Mitchener, Pharm.D. | 44 | Senior Vice President, Chief Business Officer | | Stuart Poulton | 50 | Executive Vice President, Chief Development Officer | | Reshma Rangwala, M.D., Ph.D | 45 | Executive Vice President, Chief Medical Officer | [Risk Factors](index=46&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks, primarily related to its substantial dependence on the commercial success of XPOVIO, intense competition, potential clinical trial failures, regulatory challenges, financial losses, third-party reliance, and intellectual property protection issues - **Commercialization Risks:** The business is substantially dependent on the commercial success of XPOVIO. Failure to achieve widespread market acceptance, substantial competition from existing and new therapies, and potential for serious adverse side effects could materially harm the business[283](index=283&type=chunk)[287](index=287&type=chunk)[297](index=297&type=chunk) - **Clinical and Regulatory Risks:** Clinical development is lengthy, expensive, and uncertain. Trials may fail to demonstrate safety and efficacy, and regulatory approval processes are unpredictable. Post-approval requirements, such as confirmatory trials for accelerated approvals, must be met to maintain marketing authorization[292](index=292&type=chunk)[325](index=325&type=chunk)[336](index=336&type=chunk) - **Financial Risks:** The company has a history of significant losses (**$1.3 billion accumulated deficit** as of Dec 31, 2022) and may never achieve profitability. It will need additional funding, and failure to raise capital could force a reduction in R&D or commercialization efforts. Existing debt and royalty agreements contain restrictive covenants[416](index=416&type=chunk)[420](index=420&type=chunk)[425](index=425&type=chunk) - **Third-Party Dependence:** Karyopharm relies completely on third parties for manufacturing, on partners for ex-U.S. commercialization, and on CROs for clinical trials. Any failure by these third parties to perform could disrupt operations and delay development[434](index=434&type=chunk)[442](index=442&type=chunk)[450](index=450&type=chunk) - **Intellectual Property Risks:** The inability to obtain and maintain sufficient patent protection for products could allow competitors to develop similar drugs. The company may also become involved in expensive and time-consuming lawsuits to protect or defend its IP rights[456](index=456&type=chunk)[463](index=463&type=chunk) [Unresolved Staff Comments](index=90&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) Not applicable [Properties](index=90&type=section&id=Item%202.%20Properties) The company's headquarters are located in Newton, Massachusetts, where it leases 98,502 square feet of office and laboratory space, with additional smaller office spaces leased in Munich, Germany, and Tel Aviv-Yafo, Israel - Headquarters are in Newton, Massachusetts, with **98,502 sq. ft.** of leased office and lab space[507](index=507&type=chunk) - Additional leased office spaces are located in Munich, Germany (**3,681 sq. ft.**) and Tel Aviv-Yafo, Israel (**4,736 sq. ft.**)[507](index=507&type=chunk) [Legal Proceedings](index=90&type=section&id=Item%203.%20Legal%20Proceedings) Information regarding legal proceedings is incorporated by reference from Note 11 of the Consolidated Financial Statements - The company refers to Note 11 "Commitments and Contingencies" for information on legal proceedings[508](index=508&type=chunk) [Mine Safety Disclosures](index=90&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable PART II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=91&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on the Nasdaq Global Select Market under the symbol "KPTI", with 18 holders of record as of February 10, 2023, and no cash dividends paid or anticipated - The company's common stock trades on the Nasdaq Global Select Market under the symbol "KPTI"[512](index=512&type=chunk) - As of February 10, 2023, there were **18 holders of record** of the common stock[512](index=512&type=chunk) - The company has never paid cash dividends and does not anticipate paying any in the foreseeable future[513](index=513&type=chunk) [Reserved](index=92&type=section&id=Item%206.%20%5BReserved%5D) This item is reserved [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=93&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) For the year ended December 31, 2022, Karyopharm reported total revenue of $157.1 million, a net loss of $165.3 million, and $278.0 million in cash, cash equivalents, and investments, expected to fund operations for at least the next twelve months Financial Highlights (2022 vs. 2021) | Metric | 2022 ($M) | 2021 ($M) | Change | | :--- | :--- | :--- | :--- | | **Total Revenue** | $157.1 | $209.8 | (25%) | | Net Product Revenue | $120.4 | $98.4 | +22% | | License & Other Revenue | $36.6 | $111.4 | (67%) | | **Net Loss** | ($165.3) | ($124.1) | +33% | | R&D Expenses | $148.7 | $160.8 | (8%) | | SG&A Expenses | $145.4 | $143.8 | +1% | - The **22% increase in net product revenue** in 2022 was driven by a growing number of patients treated in earlier lines of therapy and an improved net price for XPOVIO[539](index=539&type=chunk) - The decrease in license and other revenue was primarily due to the recognition of a **one-time $75.0 million upfront payment** from Menarini in 2021[540](index=540&type=chunk) - As of December 31, 2022, the company had **$278.0 million in cash, cash equivalents, and investments**, deemed sufficient to fund operations for at least the next **12 months**[527](index=527&type=chunk)[553](index=553&type=chunk) [Quantitative and Qualitative Disclosures about Market Risk](index=101&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) The company's primary market risk stems from interest rate sensitivity on its $278.0 million investment portfolio and foreign currency exchange rate fluctuations from international contracts, with no current hedging strategies in place - Primary market risk exposure is interest rate sensitivity on its **$278.0 million portfolio** of cash, cash equivalents, and investments as of December 31, 2022[569](index=569&type=chunk) - The company is also exposed to foreign currency exchange rate risk from contracts with CROs and CMOs in Canada and Europe, but does not currently use hedging instruments[571](index=571&type=chunk) [Financial Statements and Supplementary Data](index=101&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section contains the company's audited consolidated financial statements for 2022, 2021, and 2020, along with the report of the independent registered public accounting firm, Ernst & Young LLP - This item includes the audited consolidated financial statements and the report of the independent registered public accounting firm[572](index=572&type=chunk) [Controls and Procedures](index=101&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2022, a conclusion affirmed by an unqualified opinion from Ernst & Young LLP - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2022[574](index=574&type=chunk) - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2022, based on the COSO 2013 framework[576](index=576&type=chunk) - The independent registered public accounting firm issued an unqualified opinion on the company's internal control over financial reporting as of December 31, 2022[582](index=582&type=chunk)[583](index=583&type=chunk) [Other Information](index=104&type=section&id=Item%209B.%20Other%20Information) None [Disclosure Regarding Foreign Jurisdictions that Prevent Inspections](index=104&type=section&id=Item%209C.%20Disclosure%20Regarding%20Foreign%20Jurisdictions%20that%20Prevent%20Inspections) Not applicable PART III [Directors, Executive Officers and Corporate Governance](index=105&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) Information regarding directors, executive officers, and corporate governance is incorporated by reference from the company's 2023 Proxy Statement - Information for this item is incorporated by reference from the definitive proxy statement for the 2023 annual meeting of stockholders[593](index=593&type=chunk)[594](index=594&type=chunk) [Executive Compensation](index=105&type=section&id=Item%2011.%20Executive%20Compensation) Information required by this item regarding executive compensation is incorporated by reference from the company's 2023 Proxy Statement - Information for this item is incorporated by reference from the definitive proxy statement for the 2023 annual meeting of stockholders[593](index=593&type=chunk)[596](index=596&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=105&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) Information required by this item regarding security ownership is incorporated by reference from the company's 2023 Proxy Statement - Information for this item is incorporated by reference from the definitive proxy statement for the 2023 annual meeting of stockholders[593](index=593&type=chunk)[597](index=597&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=105&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) Information required by this item regarding related transactions and director independence is incorporated by reference from the company's 2023 Proxy Statement - Information for this item is incorporated by reference from the definitive proxy statement for the 2023 annual meeting of stockholders[593](index=593&type=chunk)[598](index=598&type=chunk) [Principal Accountant Fees and Services](index=105&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services) Information required by this item regarding principal accountant fees and services is incorporated by reference from the company's 2023 Proxy Statement - Information for this item is incorporated by reference from the definitive proxy statement for the 2023 annual meeting of stockholders[593](index=593&type=chunk)[599](index=599&type=chunk) PART IV [Exhibits and Financial Statement Schedules](index=106&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists the financial statements filed as part of the report and the exhibits required by Item 601 of Regulation S-K, which are listed in the Exhibit Index - This item lists the financial statements and exhibits filed with the Form 10-K[602](index=602&type=chunk)[605](index=605&type=chunk) [Form 10-K Summary](index=106&type=section&id=Item%2016.%20Form%2010-K%20Summary) None

Karyopharm Therapeutics, Inc. (NASDAQ:KPTI) Q4 2022 Earnings Conference Call February 15, 2023 8:00 AM ET Company Participants Elhan Webb - SVP, IR Richard Paulson - President, CEO & Director Sohanya Cheng - EVP & Chief Commercial Officer Reshma Rangwala - Chief Medical Officer Michael Mason - EVP, CFO & Treasurer Conference Call Participants Peter Lawson - Barclays Bank Maurice Raycroft - Jefferies Nicole Gabreski - Piper Sandler & Co. Michael Ulz - Morgan Stanley Edward White - H.C. Wainwright & Co. Eric ...

Selinexor Can Inhibit Multiple Targets of the JAK Pathway, Enabling Independent Suppression of MF cells and Potentially Complementing the Function of JAKi's1,2,3,4,5 | --- | --- | --- | --- | --- | --- | |---------------------------------------------------------------|-------------------------------------------------------------|-------|--------------------------------------------------------------------------|-------|-------| | MF is driven by upstream mutations JAK2, CALR MPL \nof or | | Par-4 | Additiona ...