• Company to Initiate a Global Randomized Clinical Trial to Treat Patients with COVID-19
• XPO1 Inhibitors have Previously Demonstrated Pre­clin­i­cal Activity Against Numerous Respiratory Viruses (Including SARS-CoV) and Asso­ci­ated Inflammation
• BOSTON sNDA Submission on Target for Q2 2020
• Management to Host Conference Call Today at 8:30 AM ET

Newton, MA (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI) to­day announced plans to ini­ti­ate a global ran­dom­ized clin­i­cal trial for low dose oral selinexor in hos­pi­talized patients with severe COVID-19. Selinexor, mar­keted as XPOVIO®, is cur­rent approved at higher doses by the Food and Drug Admin­istra­tion (FDA) as a treat­ment for patients with re­lapsed or re­frac­tory multiple myeloma. Selinexor is an oral, selective in­hib­i­tor of nuclear export (SINE) com­pound which blocks the cellular pro­tein XPO1. In addi­tion to its roles in cancer, XPO1 also facilitates the transport of several viral pro­teins from the nucleus of the host cell to the cytoplasm¹, and it amplifies the ac­­tiv­i­ties of pro-inflammatory transcription factors. SINE com­pounds have been shown to disrupt the rep­li­ca­tion of multiple viruses in vitro and in vivo. They have also been shown to mediate anti-in­flam­ma­tory and anti-viral effects, in­clud­ing res­pira­tory in­fec­tions, in several animal models. In particular, SINE com­pounds have recently been identified as having the poten­tial to in­ter­fere with key host pro­tein inter­actions with SARS-CoV-2, the virus that causes COVID-19.²

Selinexor is cur­rent the only XPO1 in­hib­i­tor approved for commercial use by the FDA and has been extensively tested in clin­i­cal trials across numerous cancer in­di­ca­tions world­wide since 2012. The proposed clin­i­cal trial to treat hos­pi­talized patients with COVID-19 would be the first study of an XPO1 in­hib­i­tor in patients with severe viral in­fec­tions.

“While Karyo­pharm’s clin­i­cal de­vel­op­ment strat­e­gy until now has been focused on patients with var­i­ous types of cancer, there is in­creas­ing evi­dence that XPO1 inhibition could play an im­por­tant role in the treat­ment of patients with viral in­fec­tions in­clud­ing SARS-CoV-2,” said Sharon Shacham, PhD, MBA, Pres­i­dent and Chief Scientific Officer of Karyo­pharm. “As the medical com­munity is urgently seek­ing inno­va­tive ways to address the COVID-19 pandemic, based on recent scientific data, we have decided to eval­u­ate the poten­tial for selinexor in the treat­ment of patients with COVID-19. We look for­ward to work­ing with clin­i­cal in­ves­ti­ga­tors and regulators across the globe as expeditiously as possible to de­ter­mine the next steps for this new ini­tia­tive. Additionally, we con­tinue to move our on­col­ogy pro­grams for­ward in­clud­ing the ex­pec­ted sub­mission of our BOSTON supple­mental New Drug Application (sNDA) in the sec­ond quarter of this year.”

“Given the globally dev­as­tat­ing impact of the COVID-19 pandemic, inno­va­tive strategies and col­lab­o­rative efforts are critically needed to bring effective treat­ment options to patients, who are so des­per­ately in need. I am highly en­cour­aged by the scientific rationale of studying selinexor, which targets both virus and immune-mediated injury, for treat­ment of patients with severe COVID-19. My staff, colleagues, and I and look for­ward to work­ing with Karyo­pharm to better under­stand the role of this novel ap­proach in im­prov­ing patient out­comes of COVID19,” said Thomas J. Walsh, MD, Pro­fessor of Medicine, Pediatrics, and Microbiology & Immunology, Weill Cornell Medicine, Cornell University.

SINE XPO1 in­hib­i­tors have dem­onstrated ac­­tiv­ity against over 20 dif­fer­en­t viruses, in­clud­ing the RNA viruses, influenza, res­pira­tory syncytial virus (RSV) and other common causes of res­pira­tory in­fec­tion. XPO1 inhibition has been identified in several assays as having poten­tial ac­­tiv­ity against SARS-CoV-2, although spe­cif­ic animal models have not been avail­able to date. One of the most im­por­tant as­pects of COVID-19 is the marked pul­mo­nary inflammation with high levels of cytokines such as IL6, IL1, IFNg and others. Along these lines, selinexor and other SINE com­pounds have dem­onstrated potent anti-in­flam­ma­tory ac­­tiv­ity through the inhibition of Nuclear Factor kB (NF-kB), leading to re­duc­tions in all of these cytokines in a variety of models, and this may be particularly beneficial to hos­pi­talized patients with COVID-19.

Karyopharm’s clin­i­cal pro­gram in COVID-19 is not ex­pec­ted to impact the timing or prioritization of other key Com­pany mile­stones, in­clud­ing the planned sub­mission of a sNDA for XPOVIO (seli­nexor) in com­bi­na­tion with once-weekly Velcade® (bor­tez­o­mib) and low-dose dexa­meth­a­sone as a new sec­ond line treat­ment for patients with re­lapsed or re­frac­tory multiple myeloma (based on the BOSTON Phase 3 trial), which remains on schedule for the sec­ond quarter of 2020. Additionally, Karyo­pharm has suf­fi­cient supply of selinexor for current and ex­pec­ted commercial supply for patients with multiple myeloma, for ongoing clin­i­cal trials in patients with var­i­ous cancers, as well as for this proposed study in patients with COVID-19.

About COVID-19 and the Potential Role of XPO1 Inhibition

The novel coronavirus SARS-CoV-2 that emerged from the Wuhan region of China in De­cem­ber 2019 shares similarity to the original SARS coronavirus, SARS-CoV.³ SARS-CoV was responsible for a 2003 human outbreak of res­pira­tory dis­ease. As such, the wealth of re­search that has been per­formed to date on SARS-CoV can serve as im­por­tant data for predicting the be­havior of SARS-CoV-2, which causes COVID-19. The role of XPO1 (also called CRM1) in SARS-CoV rep­li­ca­tion and pathogenesis was first described in 2009.⁴ XPO1 is solely responsible for exporting cer­tain SARS-CoV pro­teins, in­clud­ing 9b⁵, N⁶, S⁷, Orf3⁴ and Orf6⁸ out of the nucleus. Blockade of XPO1 is there­fore ex­pec­ted to inhibit viral assembly. In a recent analysis using VIPER-based identi­fi­ca­tion of Master Regulator pro­teins, selinexor was ranked in the top 18 of more than 400 screened drugs (top 4.5%) for inter­fer­ing with virus-host inter­action in SARS-CoV infected bronchial epithelial cells.⁹ In another study, verdi­nexor, one of Karyo­pharm’s inves­ti­ga­tional drugs that is highly similar in structure and biological ac­­tiv­ity to selinexor, was identified as a drug with the poten­tial to pharmacologically in­ter­fere with the inter­actions of several of the SARS-CoV-2 pro­teins with their human targets, and was rec­om­mended for evaluation in the treat­ment of SARS-CoV-2 viral in­fec­tion.² Similarly, a recent bio­in­for­matics study identified XPO1 together with three other pro­teins, in­clud­ing NPM1, HNRNPA1 and JUN, as “hub pro­teins” with the highest number of functional connections within 119 host pro­teins that inter­act with the human SARS-CoV.¹⁰ Of note, both NPM1 and HNRNPA1 inter­act directly with XPO1 in nor­mal cells, and JUN is in­volve­d in in­flam­ma­tory re­sponses, in­clud­ing those asso­ci­ated with viral in­fec­tions.

Severe influenza in­fec­tion shares many of the features of SARS-CoV in­fec­tion. Verdi­nexor dem­onstrated potent inhibition of influenza viral rep­li­ca­tion, even when given four days post-infection (Figure 1).^11,12 In addi­tion, verdi­nexor induced re­duc­tions in markers of dis­ease pathology and im­proved sur­vival in influenza models in mice and ferrets (Figure 1).^11,12

Figure 1: In a mouse H1N1 influenza model, delayed (up to 4 days) verdi­nexor treat­ment: (A) sig­nif­i­cantly reduces influenza virus levels; (B) ameliorated lung injury; and (C) im­proved sur­vival is avail­able at https://www.globenewswire.com/NewsRoom/AttachmentNg/ea80c453-8192-4bea-b8f8-74f7ff5670d2

XPO1 is also responsible for the nuclear export and functional inactivation of several of the major anti-in­flam­ma­tory, antioxidant and cytoprotective transcription factors in­clud­ing IkB, PPARg, RXRa, HMGB1 and Nrf2.¹³ Conversely, blockade of XPO1 leads to nuclear retention and functional activation of these critical pro­teins. High levels of XPO1 are found in multiple in­flam­ma­tory con­di­tions and may amplify ongoing in­flam­ma­tory re­sponses leading to severe organ, in­clud­ing pul­mo­nary, damage.¹⁴ In a mouse model for sepsis, selinexor treat­ment in­creased sur­vival fol­low­ing a lethal dose of endotoxin (Figure 2).¹⁵

Figure 2: In a lipopolysaccharide (LPS)-induced sepsis model, selinexor (A) attenuated lung injury, (B) reduced serum cytokines levels, (C) reduced macrophage and polymorphonuclear (PMN) subpopulations in the peritoneal exudate and im­proved sur­vival is avail­able at https://www.globenewswire.com/NewsRoom/AttachmentNg/964c3643-480c-4cc0-a7df-5b2165502349

In addi­tion, selinexor reduced in­flam­ma­tory cytokine secretion in­clud­ing TNFa, IL-6 and IFNg while reducing the numbers of macrophage and polymorphonuclear neu­tro­phils in the mice peritoneal cavity (the site of the LPS in­jec­tion).¹⁵ Importantly, treat­ment with selinexor attenuated the acute res­pira­tory distress syn­drome (ARDS)-like lung injury observed in this model. Selinexor thera­peutic effects were achieved through the inhibition of the in­flam­ma­tory NFkB path­way, induction of the anti-in­flam­ma­tory effects of the DNA binding pro­tein HMGB1 by inducing its nuclear retention and re­duc­tions in cytokine levels in­clud­ing TNF-a and IL-6.¹⁵ These findings are sig­nif­i­cant as COVID-19 dis­ease severity in­clud­ing res­pira­tory symp­toms correlates with the patient’s cytokine levels. Severe dis­ease is char­ac­ter­ized by in­creased interleukin (IL)-2, IL-7, granulocyte-colony stim­u­lating factor, interferon-γ inducible pro­tein 10, monocyte chemoattractant pro­tein 1, macrophage in­flam­ma­tory pro­tein 1-α, and tumor necrosis factor-α.¹⁶ Moreover, predictors of fatality of 150 con­firmed COVID-19 cases in Wuhan in­cluded elevated IL-6 (p<0.0001).¹⁷

Together, these results sug­gest that SINE com­pounds such as selinexor could provide both anti-viral and anti-in­flam­ma­tory ac­­tiv­i­ties in patients suffer­ing from severe COVID-19 and there­fore warrants clin­i­cal in­ves­ti­ga­tion.

Conference Call Information

Karyopharm will host a conference call to­day, Tuesday, April 7, 2020, at 8:30 a.m. Eastern Time, to discuss selinexor as a poten­tial treat­ment for hos­pi­talized patients with COVID-19. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 min­utes prior to the start time and refer to conference 6734579. A live audio webcast of the call will be avail­able under "Events & Presentations" in the Investor section of the Com­pany's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be avail­able on the Com­pany's website approx­i­mately two hours after the event.

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. Karyo­pharm re­ceived ac­cel­er­ated U.S. Food and Drug Admin­istra­tion (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. A supple­mental New Drug Application was sub­mitted to the FDA seek­ing ac­cel­er­ated ap­­prov­al for selinexor as a new treat­ment for patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL), and selinexor has re­ceived Fast Track and Orphan desig­na­tion and Priority Review from the FDA with a scheduled PDUFA date of June 23, 2020 for this patient pop­u­la­tion. 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), for which Karyo­pharm announced pos­i­tive top-line results in March 2020. Additional, ongoing trials for selinexor in­clude as a poten­tial back­bone ther­apy in com­bi­na­tion with approved myeloma ther­a­pies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or cur­rent 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.

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

IMPORTANT SAFETY INFORMATION

Thrombocytopenia

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 reac­tion.

Neutropenia

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 / Vomiting

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 event was 5 days.

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.

Diarrhea

Diarrhea was reported as an adverse reac­tion in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients treated with XPOVIO. The median time to onset of diarrhea was 15 days. Manage diarrhea by dose mod­i­fi­ca­tions and/or standard anti-diarrheal agents; admin­ister in­tra­venous fluids to prevent dehydration in patients at risk.

Anorexia / Weight Loss

Anorexia was reported as an adverse reac­tion in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. The median time to onset of anorexia was 8 days.

Weight loss was reported as an adverse reac­tion in 47% of patients, and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days.

Monitor patient weight at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Manage anorexia and weight loss with dose mod­i­fi­ca­tions, appetite stimulants, and nutritional sup­port.

Hyponatremia

XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO ex­peri­enced hyponatremia, 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, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clin­i­cal guidelines (intravenous saline and/or salt tablets), in­clud­ing dietary review. Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Infections

In patients re­ceiv­ing XPOVIO, 52% of patients ex­peri­enced any grade of in­fec­tion. Upper res­pira­tory tract in­fec­tion of any grade occurred in 21%, pneu­monia in 13%, and sepsis in 6% of patients. Grade ≥3 in­fec­tions were reported in 25% of patients, and deaths resulting from an in­fec­tion occurred in 4% of patients. The most commonly 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. Most in­fec­tions were not asso­ci­ated with neu­tro­penia and were caused by non-opportunistic organisms.

Neurological Toxicity

Neurological toxicities occurred in patients treated with XPOVIO.

Neurological adverse reac­tions 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 treated with XPOVIO. Median time to the first event was 15 days.

Optimize hydration status, hemoglobin level, and con­com­i­tant med­i­ca­tions to avoid exacerbating dizzi­ness or mental status changes.

Embryo-Fetal Toxicity

Based on data from animal studies and its mech­a­nism of action, XPOVIO can cause fetal harm when admin­istered to a pregnant woman. Selinexor admin­istra­tion to pregnant animals during or­gano­gen­e­sis resulted in structural ab­nor­mal­i­ties and alterations to growth at exposures below those occurring clin­i­cally at the rec­om­mended dose.

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 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.

The treat­ment dis­con­tinu­a­tion rate due to adverse reac­tions was 27%; 53% of patients had a re­duc­tion in the XPOVIO dose, and 65.3% had the dose of XPOVIO interrupted. The most fre­quent adverse reac­tions requiring perma­nent dis­con­tinu­a­tion in 4% or greater of patients who re­ceived XPOVIO in­cluded fatigue, nausea, and thrombo­cyto­penia. The rate of fatal adverse reac­tions was 8.9%.

Please see XPOVIO Full Prescribing Information avail­able at www.XPOVIO.com.

About Karyo­pharm Thera­peutics

Karyopharm Thera­peutics Inc. (Nasdaq: KPTI) is an on­col­ogy-focused pharma­ceu­tical com­pany dedicated to the discovery, de­vel­op­ment, and com­mer­cial­iza­tion of novel first-in-class drugs directed against nuclear export and related targets for the treat­ment of cancer and other major dis­eases. Karyo­pharm's Selective Inhibitor of Nuclear Export (SINE) com­pounds function by binding with and inhibiting the nuclear export pro­tein XPO1 (or CRM1). Karyo­pharm’s lead com­pound, XPOVIO® (seli­nexor), re­ceived ac­cel­er­ated ap­­prov­al from the U.S. Food and Drug Admin­istra­tion (FDA) in July 2019 in com­bi­na­tion with dexa­meth­a­sone as a treat­ment for patients with heavily pre­treated multiple myeloma. A Marketing Authori­za­tion Application for selinexor is also cur­rent under review by the European Medicines Agency. A supple­mental New Drug Application was recently ac­cepted by the FDA seek­ing ac­cel­er­ated ap­­prov­al for selinexor as a new treat­ment for adult patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL). In addi­tion to single-agent and com­bi­na­tion ac­­tiv­ity against a variety of human cancers, SINE com­pounds have also shown biological ac­­tiv­ity in models of neurodegeneration, inflammation, auto­immune dis­ease, cer­tain viruses and wound-healing. Karyo­pharm has several inves­ti­ga­tional pro­grams in clin­i­cal or pre­clin­i­cal de­vel­op­ment. For more in­for­ma­tion, please visit www.karyopharm.com.

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 ex­pec­ta­tions and plans relating to selinexor as a poten­tial treat­ment for hos­pi­talized patients with severe COVID-19; the initiation and design of a global ran­dom­ized clin­i­cal trial to study this poten­tial appli­ca­tion of selinexor, in­clud­ing the dosing regi­men; sub­missions to, and the review and poten­tial ap­­prov­al of selinexor in this in­di­ca­tion by, regu­la­tory author­i­ties, in­clud­ing the antic­i­pated avail­a­bil­ity of data to sup­port such sub­missions, timing of such sub­missions and actions by regu­la­tory author­i­ties and the poten­tial avail­a­bil­ity of ac­cel­er­ated ap­­prov­al path­ways; and the thera­peutic poten­tial of and poten­tial clin­i­cal de­vel­op­ment plans for Karyo­pharm’s drug can­di­dates, in­clud­ing the impact of a selinexor clin­i­cal trial on the timing or prioritization of other key com­pany mile­stones, such as its ex­pec­ted sub­mission of a supple­mental new drug appli­ca­tion in the sec­ond quarter of 2020 for XPOVIO in com­bi­na­tion with once-weekly Velcade® and low dose dexa­meth­a­sone. 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 com­plete nec­es­sary clin­i­cal de­vel­op­ment phases of selinexor in this in­di­ca­tion; that data from a clin­i­cal trial of selinexor would sup­port its use in treat­ment of hos­pi­talized patients with severe COVID-19; that regulators will approve the use of selinexor in hos­pi­talized patients with severe COVID-19, or that such ap­­prov­al will be made on an ac­cel­er­ated timeline. 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 risk that the COVID-19 pandemic could disrupt Karyo­pharm’s business more severely than it cur­rent antic­i­pates, in­clud­ing by reducing sales of XPOVIO, interrupting or delaying re­search and de­vel­op­ment efforts, impacting the ability to procure suf­fi­cient supply for the de­vel­op­ment and com­mer­cial­iza­tion of selinexor or other prod­uct can­di­dates, delaying ongoing or planned clin­i­cal trials, impeding the execution of business plans, planned regu­la­tory mile­stones and timelines, or inconveniencing patients; the adoption of selinexor for treat­ment of COVID-19 in the commercial mar­ket­place, the timing and costs in­volve­d in com­mer­cial­iz­ing selinexor for such in­di­ca­tion or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory ap­­prov­al; the ability to retain regu­la­tory ap­­prov­al of selinexor for such in­di­ca­tion or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory ap­­prov­al; Karyo­pharm's results of clin­i­cal trials and pre­clin­i­cal studies, in­clud­ing sub­se­quent analysis of existing data and new data re­ceived from ongoing and future studies; 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 studies; 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 obtain and main­tain requisite regu­la­tory ap­­prov­als and to en­roll patients in its clin­i­cal trials; unplanned cash requirements and ex­pen­di­tures; de­vel­op­ment of drug can­di­dates by Karyo­pharm’s com­pet­i­tors for in­di­ca­tions in which Karyo­pharm is cur­rent devel­op­ing its drug can­di­dates; and Karyo­pharm’s ability to obtain, main­tain and enforce patent and other in­tel­lec­tual property pro­tec­tion for any drug can­di­dates it is devel­op­ing. 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, 2019, which was filed with the Se­cu­ri­ties and Ex­change Com­mis­sion (SEC) on Feb­ru­ary 26, 2020, 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.

Velcade® is a registered trademark of Takeda Pharma­ceu­tical Com­pany Limited.

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Source: Karyo­pharm.