On December 4, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported updated results from its Phase 2b STORM study of selinexor (KPT-330), including robust rates and duration of response, compelling overall survival and a favorable safety profile, in patients with heavily pretreated refractory multiple myeloma (MM) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2016 annual meeting held December 3-6, 2016 in San Diego (Filing, 8-K, Karyopharm, DEC 4, 2016, View Source [SID1234516967]). Selinexor is the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export (SINE) compound, in development for the treatment of a variety of malignancies, including MM and acute myeloid leukemia (AML).

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"The data presented today further support the rationale for selinexor as a promising new treatment for patients with refractory myeloma with no clearly beneficial treatment options," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Based on the exciting STORM data and the existing unmet medical need, we have expanded the study to include additional patients with penta-refractory myeloma and expect to report top-line data from this study in early 2018."
Updated Phase 2b STORM Clinical Data in Refractory Multiple Myeloma

In an oral presentation titled, "Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study," Dan T. Vogl, MD, MSCE, Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, presented updated clinical data from the ongoing Phase 2b STORM study, a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in patients with quad-refractory or penta-refractory myeloma. Patients with quad-refractory disease have previously received two proteasome inhibitors (PIs) (bortezomib (Velcade) and carfilzomib (Kyprolis)) and two immunomodulatory drugs (IMiDs) (lenalidomide (Revlimid) and pomalidomide (Pomalyst)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy. Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex) or isatuximab.

Phase 2b STORM Efficacy

Category
N1 ORR (%) CBR (%) VGPR (%) PR (%) MR (%) SD (%) PD (%) NE (%)
Overall
78 16 (21% ) 26 (33% ) 4 (5% ) 12 (15% ) 10 (13% ) 27 (35% ) 9 (12% ) 16 (21% )
Quad
48 10 (21% ) 14 (29% ) 2 (4% ) 8 (17% ) 4 (8% ) 21 (44% ) 4 (8% ) 9 (19% )
Penta
30 6 (20% ) 12 (40% ) 2 (7% ) 4 (13% ) 6 (20% ) 6 (20% ) 5 (17% ) 7 (23% )
6 Doses/month
51 10 (20% ) 15 (29% ) 3 (6% ) 7 (14% ) 5 (10% ) 21 (41% ) 4 (8% ) 11 (2% )
8 Doses/month
27 6 (22% ) 11 (41% ) 1 (4% ) 5 (19% ) 5 (19% ) 6 (22% ) 5 (19% ) 5 (19% )
ORR=Objective Response Rate (VGPR+PR), CBR=Clinical Benefit Rate (VGPR+PR+MR), VGPR=Very Good Partial Response,
PR=Partial Response, MR=Minor Response, SD=Stable Disease, PD=Progressive Disease, NE=Non-Evaluable
1 One patient not included, did not have active myeloma

1
LOGO Targeting Disease at the Nuclear Pore

All responses were adjudicated by an Independent Review Committee (IRC). Among the 78 evaluable patients (median seven prior treatment regimens), the overall response rate (ORR) was 21%, and included very good partial responses (VGPR) and partial responses (PR). Among the 48 patients in the quad-refractory group, the ORR was 21%. For comparison, in a similar quad-refractory patient population, the anti-CD38 monoclonal antibodies Darzalex and isatuximab had ORRs of 21% and 20%, respectively. Among the 30 patients in the penta-refractory group, the ORR was 20%. Clinical benefit rate (ORR + MR) was 32% (all patients), 29% (quad-refractory), and 37% (penta-refractory). To the Company’s knowledge, no other agents have reported response rates in patients with penta-refractory MM. Median overall survival (OS) was 9.3 months for all patients, greater than 11 months (median not reached) for patients with ³MR, and 5.7 months for patients who did not have any response (£SD). Median duration of response (DOR) was 5 months. Grade ³3 cytopenias were the most common side effects and were generally not associated with clinical sequellae. Nausea, anorexia and fatigue were the most common non-hematological side effects, primarily Grades 1 and 2, and were treatable with supportive care and/or dose modification. There were low rates of Grade ³3 non-hematologic toxicities, with no new safety signals identified. In particular, there was one reported case of Grade 4 infection (1.3%), one case of Grade 2 neuropathy (1.3%) and one reported case of sepsis (1.3%).
Dr. Vogl commented, "The quad- and penta-refractory populations are continuing to expand as patients live longer and cycle through a variety of treatment options, including immunomodulatory drugs, proteasome inhibitors, or anti-CD38 monoclonal antibodies, before their disease ultimately becomes refractory and non-responsive. In my experience, selinexor is the first agent to be specifically investigated in in this difficult to treat and currently underserved population. The response rate and duration suggest that selinexor has the potential to be an exciting new option for myeloma treatment."
Karyopharm to Host Multiple Myeloma-focused Dinner Reception and Webcast at ASH (Free ASH Whitepaper) 2016
On Monday, December 5, 2016, Karyopharm will host an investor and analyst dinner reception, which will feature a moderated panel discussion with recognized experts in the treatment of MM, updated selinexor data in MM, and a live Q&A session. Confirmed external speakers include:

• Daniel Auclair, PhD (Moderator), Multiple Myeloma Research Foundation

• Nizar Bahlis, MD, University of Calgary, Southern Alberta Cancer Research Institute

• Paul G. Richardson, MD, Dana Faber Cancer Institute, Jerome Lipper Multiple Myeloma Center

• Ravi Vij, MD, MBA, Washington University School of Medicine in St. Louis, Oncology Division

• Dan T. Vogl, MD, Abramson Cancer Center Clinical Research Unit, University of Pennsylvania
In addition, Michael Kauffman, MD, PhD, CEO of Karyopharm Therapeutics will be joining.
The event will take place during the ASH (Free ASH Whitepaper) 2016 annual meeting and interested parties can access a live webcast of the event beginning Monday, December 5, 2016 at 8:15 p.m. PT under "Events & Presentations" in the "Investors" section of the company’s website at View Source A replay of the webcast will be archived on the company’s website for 90 days following the event.
About Selinexor
Selinexor (KPT-330) 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

Targeting Disease at the Nuclear Pore

suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 1,800 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in acute myeloid leukemia (SOPRA), diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in early 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov.