Please see Important Safety Information throughout, and full Prescribing Information.

Treating high-risk relapsed or refractory multiple myeloma (RRMM) with XPOVIO® (selinexor)+ dexamethasone combination

the first and only FDA-approved oral XPO1 inhibitor1

Meet Thomas: Living with RRMM

INDICATIONXPOVIO in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).IMPORTANT SAFETY INFORMATION• Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia is the

leading cause of dosage modifications. Thrombocytopenia was reported in 74% of patients and was severe (Grade 3-4) in 61% of patients. The median time to onset of the first event was 22 days. Bleeding occurred in 23%, clinically significant bleeding occurred in 5%, and fatal hemorrhage occurred in <1% of patients.

Please see Important Safety Information throughout, and full Prescribing Information.2

IMPORTANT SAFETY INFORMATION (cont’d)• Thrombocytopenia (cont’d): Monitor platelet counts at baseline and throughout treatment. Monitor more frequently

during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

ASCT=autologous stem cell transplant.

Patient informationCurrent age: 67Age at diagnosis: 58Occupation: Retired bank managerInterests: Enjoys taking long walks and spending time with his 6 grandchildren Disease information: Stage 1 IgG, transplant eligible, high-risk cytogenetics 1q21 gain and t(14;16)2,3

2nd line4

KRdCarfilzomib + Lenalidomide + Dexamethasone

3rd line4

DPd Daratumumab + Pomalidomide + Dexamethasone

1st line4

Induction RVdLenalidomide + Bortezomib + Dexamethasone Followed by ASCTMaintenance VBortezomib

4th lineExplore the combination of XPOVIO® (selinexor) + dexamethasone for challenging patients like Thomas who have penta-refractory and high-risk disease1

After progressing on third-line treatment, Thomas and his healthcare team are determining his next steps

Please see Important Safety Information throughout, and full Prescribing Information.3

IMPORTANT SAFETY INFORMATION (cont’d)• Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection.

Neutropenia occurred in 34% of patients, and was severe (Grade 3-4) in 21% of patients. The median time to onset of the first event was 25 days. Febrile neutropenia was reported in 3% of patients.

Patients rapidly responded to XPOVIO® (selinexor) + dexamethasone combination at a median of 4 weeks, with some responses as early as 1 week (range: 1-10 weeks)1

IN THE STORM PART 2 CLINICAL TRIAL,

ADVERSE REACTIONS The most common Grade ≥3 adverse reactions (incidence ≥20%) were thrombocytopenia, anemia, fatigue, hyponatremia, and neutropenia.

The most common adverse reactions (incidence ≥20%) are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

*Includes stringent complete response (sCR) + complete response (CR) + very good partial response (VGPR) + partial response (PR). ORR as assessed by an Independent Review Committee (IRC) based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma was the primary efficacy endpoint in the STORM Part 2 clinical trial.

ORR=overall response rate.

4 weeks (median)Time to first response (range: 1-10 weeks)

25.3% ORRClinically significant response in challenging-to-treat patients*(95% Cl: 16.4-36.0)

1 in 4 patients in the challenging-to-treat STORM population—100% of whom were refractory to daratumumab and 57% of whom had high-risk cytogenetics—achieved a clinically

significant response to XPOVIO + dexamethasone combination

Please see Important Safety Information throughout, and full Prescribing Information.4

IMPORTANT SAFETY INFORMATION (cont’d)• Neutropenia (cont’d): Obtain white blood cell counts with differential at baseline and throughout treatment.

Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of AR.

The STORM Part 2 clinical trial enrolled challenging-to-treat patients with penta-refractory multiple myeloma, including those with high-risk cytogenetics1

In STORM Part 2, a multicenter, single-arm, open-label study, a total of 122 patients received XPOVIO® (selinexor) 80 mg in combination with dexamethasone 20 mg orally on Days 1 and 3 of every week.

The approval of XPOVIO + dexamethasone combination was based upon the efficacy and safety in a prespecified subgroup analysis of the 83 patients, whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pretreated population than in the overall trial population (N=122).

100%of patients (N=83) were refractory to• Daratumumab• Lenalidomide• Pomalidomide• Bortezomib• Carfilzomib

57%of patients had high-risk cytogeneticsIncludes any of the following:• del(17p/p53)• t(14;16)• t(4;14)• 1q21

Selinexor + dexamethasone is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as category 2A for patients who have received at least 4 prior therapies and

whose disease is refractory to at least 2 PIs, at least 2 IMiDs, and an anti-CD38 mAb4*

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma. V.4.2020. © 2020 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed August 13, 2020. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Please see Important Safety Information throughout, and full Prescribing Information.5

XPOVIO® (selinexor) is the first and only FDA-approved oral XPO1 inhibitor that gets to the cell’s core to cause cell cycle arrest and apoptosis1,5-7

IMPORTANT SAFETY INFORMATION (cont’d)• Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities.• Nausea/Vomiting: Nausea and vomiting occurred in 72% and 41% of patients, respectively. Grade 3 nausea and vomiting occurred in 9% and 4% of patients, respectively. The median time to first onset of nausea and vomiting was 3 days and 7 days, respectively.

*Cargos include tumor suppressor proteins, growth regulators, and oncoprotein mRNAs.

For illustrative purposes only.

• XPOVIO blocks XPO1 so it can’t carry cargos out of the nucleus

• The cargos accumulate in the nucleus

• This accumulation causes cell cycle arrest and apoptosis

• XPO1 is overexpressed5,6,8,9

• The nuclear export of cargos into the cytoplasm is increased8,10,11

• With these important cargos mislocalized, the cancer cell is free to grow and survive6,8,12

In this cancer cell not exposed to XPOVIO

In this cancer cell exposed to XPOVIO1,5-7

XPOVIO

Cargos*XPO1

NucleusCytoplasm

Overexpression of XPO1, a nuclear export protein, is one of the mechanisms of oncogenesis and a potential target in relapsed or refractory multiple myeloma5,6,8,9

Please see Important Safety Information throughout, and full Prescribing Information.6

Majority of adverse reactions with XPOVIO® (selinexor) + dexamethasone combination are preventable, manageable, and reversible with prophylactic treatment and dose modifications1

• Provide prophylactic concomitant treatment with a 5-HT3 receptor antagonist and other anti-nausea agents prior to and during treatment with XPOVIO

• Monitor CBC, standard blood chemistry, and body weight at baseline and during treatment as clinically indicated. Monitor more frequently during the first 3 months of treatment

• Discontinuation due to ARs occurred in 27% of patients who received XPOVIO + dexamethasone

• ARs led to XPOVIO dose interruption in 65% of patients and dose reduction in 53%

• ARs which resulted in discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia

IMPORTANT SAFETY INFORMATION (cont’d)• Nausea/Vomiting (cont’d): Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and

other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of AR. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

AR=adverse reaction, CBC=complete blood count.

Recommended dosage

DAY 1 DAY 3 TOTAL WEEKLY DOSE

80 mgK20 K20 K20 K20

80 mgK20 K20 K20 K20

160 mg

First reduction 100 mgK20 K20 K20 K20 K20 No dose 100 mg

Second reduction80 mg

K20 K20 K20 K20No dose 80 mg

Third reductionK20 K20 K20

60 mgNo dose 60 mg

PERMANENTLY DISCONTINUE

DOSE REDUCTION

= 20 mgK20

Please see Important Safety Information throughout, and full Prescribing Information.7

Three key steps to starting your patients on XPOVIO® (selinexor) + dexamethasone combination

IMPORTANT SAFETY INFORMATION (cont’d)• Diarrhea: Diarrhea occurred in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients. The median

time to onset was 15 days.

1. Set expectations1 2. Prescribe1 3. Monitor your patient1

• Counsel patients on what to expect when receiving treatment with XPOVIO + dexamethasone– Advise patients to maintain

adequate fluid and caloric intake throughout treatment

• Prescribe XPOVIO + dexamethasone combination with a 5HT3 antagonist like ondansetron and another medication for nausea and vomiting, like olanzapine or rolapitant, as referenced in NCCN Guidelines*– The NCCN Clinical Practice Guidelines

in Oncology (NCCN Guidelines®) recommends olanzapine for the prevention of nausea and vomiting13*

• Monitor CBC with differential, standard blood chemistries, body weight, nutritional status, and volume status at baseline and during treatment, more frequently during the first 3 months of treatment

• Consider intravenous hydration for patients at risk of dehydration

• Assess the need for dose modifications

*Please see Prescribing Information for dosage and administration of agents listed.

Consider how an all-oral regimen may be right for your patients with high-risk RRMM

Please see Important Safety Information throughout, and full Prescribing Information.8

IMPORTANT SAFETY INFORMATION (cont’d)• Diarrhea (cont’d): Interrupt, reduce dose, or permanently

discontinue based on severity of AR. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

• Anorexia/Weight Loss: Anorexia and weight loss occurred in 53% and 47% of patients, respectively. Grade 3 anorexia and weight loss occurred in 5% and 1% of patients, respectively. The median time to anorexia and weight loss onset was 8 and 15 days, respectively.

• Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of AR. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

• Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia occurred in 39% of patients. 22% of patients experienced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.

• Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

• Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. 52% of patients experienced any grade of infection after XPOVIO.

Grade ≥3 infections were reported in 25% of patients, and deaths from infection occurred in 4% of patients within 30 days of the last treatment. Upper respiratory tract infection of any grade occurred in 21%, pneumonia in 13%, and sepsis in 6% of patients. The most frequently reported Grade ≥3 infections were pneumonia in 9% of patients, followed by sepsis in 6%. The median time to onset was 54 days for pneumonia and 42 days for sepsis.

• Atypical infections reported after XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

• Monitor for signs and symptoms of infection, evaluate and treat promptly.

• Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities. Neurological ARs, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state) occurred in 30% of patients and severe events (Grade 3-4) occurred in 9% of patients. The median time to the first event was 15 days.

• Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

• Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

• Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

Please see Important Safety Information throughout, and full Prescribing Information.9

IMPORTANT SAFETY INFORMATION (cont’d)• Embryo-Fetal Toxicity (cont’d): Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS• The most common ARs (incidence ≥20%) were thrombocytopenia,

fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

• The treatment discontinuation rate due to ARs was 27%; 53% of patients had a reduction in the XPOVIO dose, and 65% had the dose of XPOVIO interrupted. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia. Fatal ARs occurred in 9% of patients and serious ARs occurred in 58% of patients.

References: 1. XPOVIO (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics Inc; June 2020. 2. Rajan AM, et al. Blood Cancer J. 2015;5:e365. 3. Sonneveld P, et al. Blood. 2016;127(24):2955-2962. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma. V.4.2020. © 2020 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed August 13, 2020. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Yang J, et al. PLoS One. 2014;9(7):e102983. 6. Gupta A, et al. J Thorac Oncol. 2017;12(9):1446-1450. 7. Ben-Barouch S, et al. Expert Opin Investig Drugs. 2020;29(1):15-21. 8. Sun Q, et al. Signal Transduct Target Ther. 2016;1:16010. 9. Mor A, et al. Curr Opin Cell Biol. 2014;28:28-35. 10. Gravina GL, et al. J Hematol Oncol. 2014;7:85. 11. Gandhi UH, et al. Clin Lymphoma Myeloma Leuk. 2018;18(5):335-345. 12. Tai YT, et al. Leukemia. 2014;28(1):155-165. 13. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Antiemesis, V1.2020. © 2020 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed April 2, 2020. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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.

USE IN SPECIFIC POPULATIONS • Of the 202 patients with multiple myeloma who received

XPOVIO, 49% were ≥65 years old, while 11% were ≥75 years old. No overall difference in effectiveness of XPOVIO was observed in the two age groups, when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients (44% vs 27%), higher incidence of serious ARs (70% vs 58%), and higher incidence of fatal ARs (17% vs 9%).

• The effect of end-stage renal disease (CLCR<15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown. Mild hepatic impairment had no clinically significant effect on the pharmacokinetics of XPOVIO. The effect of moderate and severe hepatic impairment on XPOVIO pharmacokinetics is unknown.

© 2020 Karyopharm Therapeutics Inc. All rights reserved. US-XPOV-02/20-00006 (10/20)

Patients rapidly responded to XPOVIO® (selinexor) + dexamethasone combination at a median of 4 weeks, with some responses as early as 1 week (range: 1-10 weeks)1

XPOVIO + dexamethasone combination achieved a 25.3% ORR in the challenging-to-treat STORM population, 100% of whom were refractory to daratumumab and 57% of whom had high-risk cytogenetics

XPOVIO is the first and only FDA-approved oral XPO1 inhibitor that selectively binds to and blocks XPO1, causing cell cycle arrest and apoptosis

Majority of adverse reactions with XPOVIO + dexamethasone combination are preventable, manageable, and reversible with prophylactic treatment and dose modifications

— The most common Grade ≥3 adverse reactions (incidence ≥20%) were thrombocytopenia, anemia, fatigue, hyponatremia, and neutropenia

— The most common adverse reactions (incidence ≥20%) are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection

— Serious ARs occurred in 58% of patients— Fatal ARs occurred in 9% of patients

Three key steps to starting your patients on treatment1. Set expectations2. Prescribe XPOVIO + dexamethasone3. Monitor your patients

XPOVIO is the only FDA-approved therapy in patients who are refractory to daratumumab, allowing you to attack multiple myeloma in a unique way