Targeting Disease at the Nuclear Pore Karyopharm Reports First Quarter 2024 Financial Results and Highlights Recent Company Progress Announces Significant Refinancing Transactions and Amends Royalty Agreement with Health

Karyopharm Reports First Quarter 2024 Financial Results and Highlights Recent Company Progress

Announces Significant Refinancing Transactions and Amends Royalty Agreement with HealthCare Royalty Extending Vast Majority of Its

Debt Maturities into 2028 and 2029, Well Beyond Expected Data Readouts and Potential Approvals from the Company s Three Phase 3 Trials, Strengthening the Company for its Next Stage of Growth

Achieves First Quarter 2024 Total Revenue of $33.1 Million and U.S. XPOVIO

(selinexor) Net Product Revenue of $26.0 Million

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

Present Updated Data from a Pre-Specified Exploratory Subgroup Analysis of the Phase 3 SIENDO Trial of Selinexor Maintenance Treatment in Patients with TP53 Wild-type Advanced/Recurrent Endometrial Cancer at

2024 ASCO Annual Meeting

Conference Call Scheduled for Today at 8:00 a.m. ET

NEWTON, Mass. May 8, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer

therapies, today reported financial results for the quarter ended March 31, 2024, and highlighted select corporate milestones and progress on its key clinical development programs.

We have taken a significant step that improves our capital structure, strengthening our opportunity to realize the full value of three potential new

indications for selinexor. We are strongly positioned for our next stage of growth, driven by our focused and rapidly advancing late-stage pipeline with expected data readouts from our three ongoing Phase 3 trials next year, said Richard

Paulson, President and Chief Executive Officer of Karyopharm.

First Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Financing Transactions

First Quarter 2024 Financial Results

Total Revenues: Total revenue for the first quarter of 2024 was $33.1 million, compared to $38.7 million for the first quarter of 2023.

Net product revenue: Net product revenue for the first quarter of 2024 was $26.0 million,

compared to $28.3 million for the first quarter of 2023.

License and other revenue: License and other revenue for the first quarter of 2024

was $7.1 million, compared to $10.4 million for the first quarter of 2023. The decrease was primarily due to $3.5 million of license-related revenue recognized from the Menarini Group (Menarini) during the three months ended

March 31, 2023, partially offset by a $1.0 million increase in revenue for the reimbursement of development-related expenses from Menarini due to a corresponding increase in the underlying expenses during the three months ended

Cost of sales: Cost of sales for the first quarter of 2024 was $1.9 million, compared to $1.4 million for the first

quarter of 2023. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

Research and development

(R&D) expenses: R&D expenses for the first quarter of 2024 were $35.4 million, compared to $32.3 million for the first quarter of 2023. The increase was primarily due to higher clinical trial costs related to the advancement of

our three pivotal Phase 3 programs during the three months ended March 31, 2024.

Selling, general and administrative (SG&A) expenses:

SG&A expenses for the first quarter of 2024 were $29.5 million, compared to $35.9 million for the first quarter of 2023. The decrease was primarily due to our ongoing cost reduction initiatives and lower headcount.

Interest income: Interest income for the first quarter of 2024 was $2.2 million, compared to $2.8 million for the first quarter of 2023.

Interest expense: Interest expense for the first quarter of 2024 was $5.9 million, compared to $5.8 million for the first quarter of 2023.

Net loss: Karyopharm reported a net loss of $37.4 million, or $0.32 per share, for the first quarter of 2024, compared to a net loss of

$34.1 million, or $0.30 per share, for the first quarter of 2023.

Cash position: Cash, cash equivalents, restricted cash and investments as

of March 31, 2024 totaled $149.3 million, compared to $192.4 million as of December 31, 2023.

2024 Financial Outlook

Based on its current operating plans, Karyopharm reaffirms the following for full year 2024:

Conference Call Information

Karyopharm will host a

conference call today, May 8, 2024, at 8:00 a.m. Eastern Time, to discuss the first quarter 2024 financial results and provide business highlights. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international)

at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under Events & Presentations in the Investor

section of the Company s website. An archived webcast will be available on the Company s website approximately two hours after the event.

About XPOVIO (selinexor)

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 U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines

of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories

and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm s global partners. Selinexor is also being investigated in several other

mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

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:

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Use In Specific Populations

Lactation: Advise not to

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

About Karyopharm Therapeutics

Karyopharm Therapeutics

Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company whose dedication to pioneering novel cancer therapies is fueled by a belief in the extraordinary strength and courage of patients with cancer. Since its founding, Karyopharm has been

an industry leader in oral compounds that address nuclear export dysregulation, a fundamental mechanism of oncogenesis. Karyopharm s lead compound and

first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO (selinexor), is approved in the U.S. and marketed by

the Company in three oncology indications. It has also received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as

NEXPOVIO ) and China. Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including in multiple myeloma, endometrial cancer, myelofibrosis, and diffuse

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; the anticipated benefits of and activities under the refinancing transactions; 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 U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the

need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of

such agreement; Karyopharm s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm s competitors for products or product

candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm s business, results of

operations and financial condition; and Karyopharm s ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates.

These and other risks are described under the caption Risk Factors in Karyopharm s Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the Securities and

Exchange Commission (SEC) on February 29, 2024, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required

by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

XPOVIO and NEXPOVIO are registered

trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners.

Senior Vice President, Investor Relations

Head of Corporate Communications

|stacy.nobles@karyopharm.com

KARYOPHARM THERAPEUTICS INC.

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

(unaudited); (in thousands, except per share amounts)

KARYOPHARM THERAPEUTICS INC.

CONDENSED CONSOLIDATED BALANCE SHEETS

(unaudited); (in thousands)