Targeting Disease at the Nuclear Pore Karyopharm Reports New and Updated Selinexor Combination Data from the Phase 1b/2 STOMP Study at the European Hematology Association 2019 Annual Meeting Once Weekly Oral Selinexor in

Karyopharm Reports New and Updated Selinexor Combination Data from the Phase 1b/2 STOMP Study at the

European Hematology Association 2019 Annual Meeting

Once Weekly Oral Selinexor in Combination with Kyprolis and Low Dose Dexamethasone Demonstrates 78% ORR in Patients with Heavily Pretreated, Kyprolis-Na ve Multiple Myeloma

Once Weekly Oral Selinexor in Combination with

Darzalex and Low Dose Dexamethasone Demonstrates 73% ORR in Patients with Heavily Pretreated, Darzalex-Na ve Multiple Myeloma

Once Weekly Oral Selinexor in Combination with Oral Pomalyst and Low Dose

Dexamethasone Demonstrates 57% ORR in Pomalyst-Na ve and Revlimid -Relapsed or -Refractory Multiple Myeloma with 12.2 Month PFS

NEWTON, Mass. June 14, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced

three presentations highlighting new and updated data from the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study evaluating selinexor, the

Company s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, and dexamethasone in combination with standard approved multiple myeloma

(MM) therapies, Kyprolis (carfilzomib), Darzalex (daratumumab), or Pomalyst (pomalidomide), in patients with previously treated multiple myeloma. The data will be featured in oral and poster presentations at the European Hematology Association (EHA) 2019 Annual

Meeting taking place June 13-16, 2019 in Amsterdam.

Preliminary data from the Kyprolis arm of the Phase

1b/2 STOMP study show early but encouraging clinical activity, including two patients who achieved a complete response, along with an expected and manageable tolerability profile, in patients with heavily pretreated, double-refractory Kyprolis-na ve multiple myeloma, said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. Additionally, the Darzalex and Pomalyst arms of the STOMP study continue to

demonstrate impressive response rates, including encouraging rates of very good partial responses (VGPR), which indicate a 90% or greater reduction in a patient s disease burden.

New Phase 1b/2 STOMP Study Data: Selinexor plus Kyprolis and Low-dose Dexamethasone (SKd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor (dosed once weekly) is being evaluated in combination with Kyprolis (56mg/m2 or 70mg/m2 once weekly) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed refractory MM who have received

at least two prior therapies, which can include previous treatment with a proteasome inhibitor (PI), one or more immunomodulatory drugs (IMiDs: Revlimid, Pomalyst) or Darzalex. All patients on the study had previously received both PIs and IMiDs.

The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (CR+VGPR+PR); SD= Stable Disease

Among the 9 patients evaluated for safety as of the data cutoff date, the most common treatment-related 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 (67%), fatigue (44%), hyperglycemia (44%), anorexia (33%) and vomiting (33%), and were mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included thrombocytopenia

(78%), leukopenia (33%), anemia (22%) and neutropenia (22%). Dose limiting toxicities, including Grades 3 and 4 thrombocytopenia, Grade 3 pneumonia and Grade 3 vomiting, were observed in patients receiving selinexor 80mg and Kyprolis 70mg/m2 and selinexor 100mg and Kyprolis 56mg/m2. No DLTs were reported in the selinexor 80mg and Kyprolis 56mg/m2 cohort, and therefore, confirmation of the recommended Phase 2 dose (RP2D) is ongoing with this dosing regimen.

Updates on Phase 1b/2 STOMP Study: SDd and SPd

Selinexor plus Darzalex and Low-dose Dexamethasone (SDd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor (dose escalated using either 100mg once weekly or 60mg twice weekly) is being evaluated in

combination with Darzalex (16mg/kg intravenously once weekly) and low dose dexamethasone (dex; orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory MM who received at least three prior lines of therapy, including a

PI and an IMiD, or patients with MM refractory to both a PI and an IMiD. The following table is a summary of the updated efficacy results:

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

Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID)-refractory disease, only one patient

(3%) did not have at least a minimal response. Median progression-free survival (PFS) has not been reached. Among patients with at least a PR, the median time on treatment was 7.7 months, while the median time on study for all evaluable patients was

4.8 months. Median time to response was 1.0 month. Based on published data, the expected ORR for Darzalex therapy without selinexor in the Darzalex-na ve population is ~29%. Thus, the ORR of 73% continues

to provide a basis for further evaluation of the SDd combination.

Among the 31 patients evaluated for safety as of the data cutoff date, the most common

treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic

treatment-related AEs were nausea (68%), fatigue (58%), anorexia (32%), insomnia (32%), diarrhea (32%), hyponatremia (32%), and vomiting (26%), and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 treatment-related AEs

were hematologic AEs and included thrombocytopenia (42%), anemia (29%), leukopenia (26%) and neutropenia (23%). No Grade 5 AEs were reported. Based on these tolerability and efficacy data, the recommended RP2D of SDd is selinexor (100mg orally, once

weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, once weekly).

Selinexor plus Pomalyst and Low-dose Dexamethasone (SPd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor (60mg or 80mg once weekly or 60mg or 80mg twice weekly) is being evaluated in combination with

Pomalyst (2mg, 3mg or 4mg orally, once daily) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory MM who received at least two prior lines of therapy, including a PI and an IMiD, or patients with

MM 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)

Among the 45 patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and

constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (56%), fatigue (53%) and anorexia (49%) and

mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included neutropenia (56%), thrombocytopenia (31%), anemia (31%) and leukopenia (16%). There were three Grade 5 treatment-related

events (febrile neutropenia, intracranial hemorrhage and pneumonia). Determination of the RP2D is still ongoing.

Details for the EHA 2019 STOMP

presentations are as follows:

Title: Safety and Efficacy of combination of Selinexor, Daratumumab, and Dexamethasone (SDd) in Patients with Multiple Myeloma (MM) Previously

Exposed to Proteasome Inhibitors and Immunomodulatory Drugs

Lead author: Cristina Gasparetto, Duke University Cancer Center

Session: Myeloma and other

monoclonal gammopathies Clinical

Date and Time: Sunday, June 16, 2019; 09:00 09:15 CEST

Location: Auditorium

Poster Presentations

Title: Selinexor, Pomalidomide, and Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Lead author: Christina Chen, Princess Margaret Cancer Center

Session: Myeloma and other

monoclonal gammopathies Clinical

Date and Time: Friday, June 14, 2019; 17:30 19:00 CEST

Location: Poster Area

Title: A Phase 1b/2 Study of Selinexor, Carfilzomib, and Dexamethasone (SKd) in Relapsed/ Refractory Multiple Myeloma (RRMM)

Lead author: Cristina Gasparetto, Duke University Cancer Center

Session: Myeloma and other

monoclonal gammopathies Clinical

Date and Time: Saturday, June 15, 2019; 17:30 19:00 CEST

Location: Poster Area

Additional selinexor

presentations at EHA 2019 are as follows:

Title: A Phase 2 Study of Selinexor Plus Cytarabine and Idarubicin in Patients with

Relapsed/Refractory Acute Myeloid Leukemia (AML)

Lead author: Walter Fiedler, Hubertus Wald University Cancer Center Hamburg

Session: Acute myeloid leukemia

Date and Time: Saturday, June 15, 2019; 17:00 17:15 CEST

Title: A Randomized,

Open-Label, Phase II Study of Selinexor Versus Physician s Choice (PC) In Older Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

Lead author: Kendra Sweet, Moffitt Cancer Center

Session: Acute myeloid leukemia

Date and Time: Friday, June 14, 2019; 17:30 19:00 CEST

Location: Poster Area

Note: As reported previously by

Karyopharm in 2017, this study did not meet its pre-specified primary endpoint.

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear

Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor

suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination

with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available.

Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm s New Drug Application (NDA) seeking accelerated approval has been accepted

for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients based on data from the STORM study. The Company has also submitted a Marketing Authorization

Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval. 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), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently