Targeting Disease at the Nuclear Pore Karyopharm Reports New and Updated XPOVIO (Selinexor) Data in Relapsed or Refractory Multiple Myeloma at the American Society of Hematology 2019 Annual Meeting All Oral Regimen of On

Karyopharm Reports New and Updated XPOVIO

(Selinexor) Data in Relapsed or

Refractory Multiple Myeloma at the American Society of Hematology

All Oral Regimen of Once Weekly Selinexor in Combination with Daily

Pomalyst and Low Dose Dexamethasone Demonstrates 56% Overall Response Rate in

Pomalyst -Na ve and Revlimid -Relapsed or -Refractory Myeloma with Progression-Free

Survival of 12.2 Months

Selinexor and Low Dose Dexamethasone Either Alone or in Combination with Velcade or Kyprolis Results in Responses in Six of Seven Patients Whose Myeloma Has Progressed Following Experimental CAR-T Therapy

NEWTON, Mass. December 7, 2019 Karyopharm Therapeutics Inc.

(Nasdaq:KPTI), an oncology-focused pharmaceutical company, today announced that two presentations highlighting new and updated data relating to XPOVIO (selinexor), the Company s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, will be given at the American Society of Hematology (ASH) 2019 Annual Meeting taking place December

7-10, 2019 in Orlando. The first study, which will be featured in an oral presentation, describes updated data from the Phase 1b/2 STOMP study evaluating the all oral regimen of selinexor in combination with

Pomalyst (pomalidomide) and low-dose dexamethasone (dex) (SPd) in patients with relapsed or refractory multiple myeloma. The second abstract, which

will be featured in a poster presentation, describes new data on the use of selinexor and dexamethasone, either alone or in combination with standard approved therapies, in patients with multiple myeloma whose disease has progressed following

experimental chimeric antigen receptor T-cell (CAR-T) therapy.

continue to be pleased with the efficacy and safety observed in the all oral selinexor plus Pomalyst arm of the Phase 1b/2 STOMP study, where patients with Pomalyst-na ve and Revlimid (lenalidomide)-relapsed or -refractory myeloma achieved a 56% overall response rate (ORR) and a 12-month progression free survival (PFS), said Sharon

Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. Another key study this year is the presentation of new data from patients treated with selinexor-based regimens after their myeloma had progressed following

experimental CAR-T therapy. Although these data are early, six of seven patients whose disease relapsed after CAR-T achieved a response when treated with selinexor and

dexamethasone alone or in combination with either Velcade (bortezomib) or Kyprolis (carfilzomib). There is currently very limited

data regarding treatment options for patients whose disease has progressed following experimental CAR-T therapy, and we believe these encouraging results further reinforce the therapeutic activity of selinexor

in patients with relapsed or refractory disease.

Updated Data from Phase 1b/2 STOMP Study Evaluating Selinexor in Combination with Pomalyst and Low-dose Dexamethasone (SPd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor is being evaluated in

combination with Pomalyst (3 or 4mg orally, once daily) and low dose dexamethasone (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory multiple myeloma who received at least three prior lines of therapy, including

a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or patients with myeloma refractory to both a PI and an IMiD. The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (VGPR+PR); VGPR=Very Good Partial Response; PR=Partial Response

Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related adverse events (AEs) were cytopenias, along with

gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (52%), fatigue

(52%) and weight loss (39%). As expected, the most common treatment-related Grade 3 and 4 AEs were neutropenia (58%), thrombocytopenia (27%) and anemia (27%).

Based on these Phase 2 results, a Phase 3 study investigating the SPd combination is planned.

In parallel with the ongoing Phase 1b/2 STOMP study, Karyopharm is conducting the pivotal, randomized Phase 3 BOSTON study evaluating once-weekly selinexor in

combination with the PI Velcade and dexamethasone (SVd) for the treatment of patients with multiple myeloma who have had one to three prior lines of therapy. Enrollment in the BOSTON study is complete and

top-line data are expected in early 2020 contingent upon the occurrence of PFS events, the primary endpoint of the study. Data from the BOSTON study, if positive, are expected to be used to support regulatory

submissions to the U.S. Food and Drug Administration and the European Medicines Agency requesting the use of selinexor in combination with Velcade and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.

New Data from Study Evaluating Selinexor in Patients with Multiple Myeloma Following CAR-T Therapy

In this study, seven patients were identified from selinexor myeloma trials who had received an active dose of CAR-T

cell therapy (>108 CAR-positive cells targeting B-cell maturation antigen) as treatment for their multiple

myeloma prior to being enrolled in a trial using a selinexor-containing regimen. One patient was treated with selinexor (starting at 80 mg twice-weekly) and dexamethasone (20 mg twice weekly), one patient was treated with the regimen currently being

investigated in the ongoing Phase 3 BOSTON study, a combination of selinexor (100 mg once-weekly), Velcade (1.3 mg/m2 once-weekly for 4 of 5 weeks) and dexamethasone (40 mg once-weekly), and five

patients were treated with a combination of selinexor (100 mg once-weekly), Kyprolis (20/56 mg/m2 or 20/70 mg/m2) and dexamethasone (40 mg once

weekly or 20 mg twice weekly). Patients had a median of ten prior therapeutic regimens (range: 5-15), all had high-risk cytogenetics, and six of the seven had rapidly progressing disease as indicated by the

percent increase in paraprotein (17-91%) between screening and Cycle 1 Day 1 (range: 7-22 days).

The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (CR+VGPR+PR); sCR=Stringent Complete Response

Of the six patients who responded ( PR), the duration of response ranged from 1.4 months to 7.4 months, with two

patients still on therapy and responding. Adverse events were consistent with what has previously been reported with selinexor-containing regimens in heavily-pretreated patients with multiple myeloma and included nausea, fatigue, thrombocytopenia,

neutropenia, and anemia.

These preliminary data suggest that selinexor-dexamethasone alone or in combination with Velcade or Kyprolis may offer a

therapeutic option for patients who have exhausted other available treatments, have rapidly progressing disease, and who have progressed after CAR-T therapy.

Details for these two ASH 2019 presentations are as follows:

Title: Selinexor, Pomalidomide,

and Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma

Presenter: Christine Chen, Princess Margaret Cancer Centre

Session: 653. Myeloma: Therapy,

excluding Transplantation: New Approaches in the Treatment of Relapsed/Refractory Plasma Cell Discrasias

Date and Time: Saturday, December 7,

2019; 9:30-11:00 AM ET

Location: Orange County Convention Center, Hall E1

Poster Presentation Company-Sponsored Studies

Title: Selinexor-Containing Regimens for the Treatment of Patients with Multiple Myeloma Refractory to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Presenter: Ajai Chari, Icahn School of Medicine at

Myeloma: Therapy, excluding Transplantation: Poster I

Date and Time: Saturday, December 7, 2019;

Location: Orange County Convention Center, Hall B

PDF copies of these presentations will be available here following conclusion of the presentations at the meeting.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE)

compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to

accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe

DNA damage to continue to grow and divide in an unrestrained fashion. In addition to receiving accelerated FDA approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment

of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least

two immunomodulatory agents, and an anti-CD38 monoclonal antibody, Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor. Selinexor is

also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase

2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has

received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple

cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone

therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), in recurrent gliomas (KING) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including

multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at

www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION

XPOVIO can cause thrombocytopenia,

leading to potentially fatal hemorrhage. Thrombocytopenia was reported as an adverse reaction in 74% of patients, and severe (Grade 3-4) thrombocytopenia occurred in 61% of patients treated with XPOVIO. The median time to onset of the first event

was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, clinically significant bleeding occurred in 5% of patients with thrombocytopenia and fatal hemorrhage occurred in <1% of patients.

Monitor platelet counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two 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 and/or reduce dose, or permanently discontinue based on severity of adverse

XPOVIO can cause neutropenia,

potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients, and severe (Grade 3-4) neutropenia occurred in 21% of patients treated with XPOVIO. The median time to onset of the first event was 25

days. Febrile neutropenia was reported in 3% of patients.

Obtain neutrophil counts at baseline, during treatment, and as clinically indicated. Monitor

more frequently during the first two months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures including antimicrobials for signs of infection and use of growth factors

(e.g., G-CSF). Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.

Gastrointestinal Toxicity

Gastrointestinal toxicities occurred in patients treated with XPOVIO.

Nausea was reported as an adverse

reaction in 72% of patients, and Grade 3 nausea occurred in 9% of patients treated with XPOVIO. The median time to onset of the first nausea event was 3 days.

Vomiting was reported in 41% of patients, and Grade 3 vomiting occurred in 4% of patients treated with XPOVIO. The median time to onset of the first vomiting

Provide prophylactic 5-HT3 antagonists and/or other anti-nausea agents, prior to and during

treatment with XPOVIO. Manage nausea/vomiting by dose interruption, reduction, and/or discontinuation. Administer intravenous fluids and replace electrolytes to prevent dehydration in patients at risk. Use additional anti-nausea medications as

clinically indicated.