PR98573

Karyopharm and Menarini Group Announce Orphan Medicinal Product Designation from the European Commission for Selinexor for the Treatment of Myelofibrosis

NEWTON, Mass. and FLORENCE, Italy, Nov. 1, 2022 /PRNewswire=KYODO JBN/ --

Karyopharm Therapeutics Inc. (NASDAQ: KPTI), a commercial-stage pharmaceutical

company pioneering novel cancer therapies, and the Menarini Group ("Menarini"),

a privately-held, leading international pharmaceutical company, today announced

that the European Commission (EC) has granted orphan medicinal product

designation for selinexor for the treatment of myelofibrosis (MF). Selinexor

was granted orphan drug designation in MF by the U. S. Food and Drug

Administration (FDA) in May 2022. Karyopharm is currently evaluating selinexor,

a first-in-class XP01 inhibitor, as monotherapy in patients with previously

treated MF, and in combination with ruxolitinib in treatment-naïve patients. In

December 2021, Karyopharm and Menarini entered into an exclusive licensing

agreement whereby Menarini is responsible for commercializing all current and

future indications of NEXPOVIO(R) in the European Economic Area, United Kingdom

and Switzerland, CIS countries, Turkey and Latin America. Stemline Therapeutics

B.V., a wholly owned subsidiary of Menarini, is leading all commercialization

activities in Europe.

"We are very pleased to receive orphan medicinal product designation from the

EC for selinexor for the treatment of myelofibrosis," said Reshma Rangwala, MD,

PhD, Chief Medical Officer of Karyopharm. "Building on our recent orphan drug

designation from the FDA, this recognition continues to reinforce the

significant unmet need for a drug with a novel mechanism of action like

selinexor for this devastating disease. Our clinical plans remain on track, and

we look forward to the continued development of selinexor in MF."

"Myelofibrosis is a difficult-to-treat and complex disorder of the bone marrow

with limited therapeutic options and we are committed to bringing novel

treatments to patients through our collaboration with Karyopharm. We are

excited about the potential to bring selinexor to myelofibrosis patients in

Europe, pending positive study read-outs and regulatory approval," said Olivia

del Puerto, MD LMS, Head of Medical Affairs Oncology - EMEA of Menarini.

About the EMA Orphan Designation

Orphan medicinal product designation in the European Union (EU) is granted by

the European Commission which adopts the positive opinion issued by the

European Medicines Agency (EMA) Committee for Orphan Medicinal Products. The

EMA's orphan designation is available to companies developing treatments for

life-threatening or chronically debilitating conditions that affect fewer than

five in 10,000 persons in the EU. Medicines that meet the EMA's orphan

designation criteria qualify for financial and regulatory incentives that

include a 10-year period of marketing exclusivity in the EU after product

approval, reduced fees and access to centralized marketing authorization.

About MF

MF is a rare type of bone marrow cancer that disrupts the body's normal

production of blood cells. It causes extensive scarring of the bone marrow,

leading to severe anemia that can cause weakness and fatigue. Bone marrow

scarring can also cause a low number of platelets, which increases the risk of

bleeding. MF affects males and females in equal numbers and can occur at any

age, although it usually affects individuals 50 years old or older. According

to the National Organization of Rare Diseases (NORD), the incidence is

estimated to be 1.5 cases per 100,000 people in the United States and in

Northern European countries, based on studies, the incidence is estimated to be

0.5 cases per 100,000 people.1

About NEXPOVIO(R) (selinexor)

NEXPOVIO(R), which is marketed as XPOVIO(R) in the U.S., has been approved in

the following oncology indications by the European Commission: (i) in

combination with dexamethasone for the treatment of multiple myeloma in adult

patients who have received at least four prior therapies and whose disease is

refractory to at least two proteasome inhibitors, two immunomodulatory agents

and an anti-CD38 monoclonal antibody, and who have demonstrated disease

progression on the last therapy; and (ii) in combination with bortezomib and

dexamethasone for the treatment of adults with multiple myeloma who have

received at least one prior therapy. The marketing authorization of NEXPOVIO is

valid in the EU Member States as well as Iceland, Liechtenstein, Norway, and

Northern Ireland. NEXPOVIO has been commercially available in Germany since

October 1, 2022.

NEXPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor. NEXPOVIO

functions by selectively binding to and inhibiting the nuclear export protein

exportin 1 (XPO1, also called CRM1). NEXPOVIO 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.

Please see NEXPOVIO(R) Summary of Product Characteristics and European Public

Assessment Report at

https://ec.europa.eu/health/documents/community-register/html/h1537.htm

Please refer to local prescribing information where XPOVIO/NEXPOVIO is approved

for full information.

IMPORTANT SAFETY INFORMATION

Contraindications: Hypersensitivity to selinexor.

Special warnings and precautions for use:

Recommended concomitant treatments

Patients should be advised to maintain adequate fluid and caloric intake

throughout treatment. Intravenous hydration should be considered for patients

at risk of dehydration.

Prophylactic concomitant treatment with a 5-HT3 antagonist and/or other

anti-nausea agents should be provided prior to and during treatment with

NEXPOVIO(R).

Haematology:

Patients should have their complete blood counts (CBC) assessed at baseline,

during treatment, and as clinically indicated. Monitor more frequently during

the first two months of treatment.

Thrombocytopenia:

Thrombocytopenic events (thrombocytopenia and platelet count decreased) were

frequently reported in adult patients receiving selinexor, which can be severe

(Grade 3/4). Patients should be monitored for signs and symptoms of bleeding

and evaluated promptly.

Neutropenia:

Severe neutropenia (Grade 3/4) has been reported with selinexor.

Patients with neutropenia should be monitored for signs of infection and

evaluated promptly.

Gastrointestinal toxicity:

Nausea, vomiting, diarrhoea, which sometimes can be severe and may require the

use of anti-emetic and anti-diarrhoeal medicinal products.

Weight loss and anorexia:

Patients should have their body weight, nutritional status and volume checked

at baseline, during treatment, and as clinically indicated. Monitoring should

be more frequent during the first two months of treatment.

Confusional state and dizziness:

Patients should be instructed to avoid situations where dizziness or

confusional state may be a problem and to not take other medicinal products

that may cause dizziness or confusional state without adequate medical advice.

Patients should be advised not to drive or operate heavy machinery until

symptoms resolve.

Hyponatraemia:

Patients should have their sodium levels checked at baseline, during treatment,

and as clinically indicated. Monitoring should be more frequent during the

first two months of treatment.

Cataract:

Selinexor can cause new onset or exacerbation of cataract. Ophthalmologic

evaluation may be performed as clinically indicated.  Cataract should be

treated as per medical guidelines, including surgery if warranted.

Tumour lysis syndrome (TLS):

TLS has been reported in patients receiving therapy with selinexor. Patients at

a high risk for TLS should be monitored closely. Treat TLS promptly in

accordance with institutional guidelines.

Fertility, pregnancy and lactation

Women of childbearing potential/contraception in males and females:

Women of childbearing potential and male adult patients of reproductive

potential should be advised to use effective contraceptive measures or abstain

from sexual intercourse while being treated with selinexor and for at least 1

week following the last dose of selinexor.

Pregnancy:

There are no data from the use of selinexor in pregnant women. Selinexor is not

recommended during pregnancy and in women of childbearing potential not using

contraception.

Breast-feeding:

It is unknown whether selinexor or its metabolites are excreted in human milk.

A risk to breast-fed children cannot be excluded. Breast-feeding should be

discontinued during treatment with selinexor and for 1 week after the last dose.

Undesirable effects

Summary of the safety profile

The most frequent adverse reactions (greater than or equal to 30%) of selinexor

in combination with dexamethasone were nausea, thrombocytopenia, fatigue,

anaemia, decreased appetite, decreased weight, diarrhea, vomiting,

hyponatraemia, neutropenia and leukopenia.

The most commonly reported serious adverse reactions (greater than or equal to

3%) were pneumonia, sepsis, thrombocytopenia, acute kidney injury, and anaemia.

Description of selected adverse reactions

Infections: Infection was the most common non-haematological toxicity. Upper

respiratory tract infection and pneumonia were the most commonly reported

infections with 25% of reported infections being serious and fatal infections

occurring in 3% of treated adult patients.

Elderly population

Patients 75 years and older had a higher incidence of discontinuation due to an

adverse reaction, higher incidence of serious adverse reactions, and higher

incidence of fatal adverse reactions.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after Authorisation of the medicinal

product is important. It allows continued monitoring of the benefit/risk

balance of the medicinal product. Healthcare professionals are asked to report

any suspected adverse reactions via the national reporting system listed in

Appendix V.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (NASDAQ: KPTI) is a commercial-stage

pharmaceutical company pioneering novel cancer therapies. Since its founding,

Karyopharm has been the industry leader in oral Selective Inhibitor of Nuclear

Export (SINE) compound technology, which was developed to address a fundamental

mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE

compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO(R)

(selinexor), is approved in the U.S. and marketed by the Company in three

oncology indications and has received regulatory approvals in various

indications in a growing number of ex-U.S. territories and countries, including

Europe and the United Kingdom (as NEXPOVIO(R)), China, Singapore, Canada,

Israel, South Korea, and Australia. Karyopharm has a focused pipeline targeting

multiple high unmet need cancer indications, including in multiple myeloma,

endometrial cancer, myelodysplastic syndromes and myelofibrosis. For more

information about our people, science and pipeline, please visit

www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn.

About Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics

company, with a turnover of over $4 billion and over 17,000 employees. Menarini

is focused on therapeutic areas with high unmet needs with products for

oncology, cardiology, pneumology, gastroenterology, infectious diseases,

diabetology, inflammation, and analgesia. With 18 production sites and 9

Research and Development centers, Menarini's products are available in 140

countries worldwide. For further information, please visit  www.menarini.com

and LinkedIn.

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 the ability of selinexor to treat patients

with multiple myeloma and expectations related to future clinical development

and potential regulatory submissions of selinexor. 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 commercialize XPOVIO(R); or that

any of Karyopharm's drug candidates, including selinexor and eltanexor, will

successfully complete necessary clinical development phases or that development

of any of Karyopharm's drug candidates will continue. 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 currently anticipates, including by negatively

impacting 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 XPOVIO in the commercial marketplace, the timing and costs involved

in commercializing XPOVIO or any of Karyopharm's drug candidates that receive

regulatory approval; the ability to obtain and retain regulatory approval of

XPOVIO 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 enroll

patients in its clinical trials; unplanned cash requirements and expenditures;

development or regulatory approval of drug candidates by Karyopharm's

competitors for products or product candidates in which Karyopharm is currently

commercializing or developing; and Karyopharm's ability to obtain, maintain and

enforce patent and other intellectual property protection for any of its

products or product candidates. These and other risks are described under the

caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the

quarter ended June 30, 2022, which was filed with the Securities and Exchange

Commission (SEC) on August 4, 2022, 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.

XPOVIO(R) and NEXPOVIO(R) are registered trademarks of Karyopharm Therapeutics

Inc. Any other trademarks referred to in this release are the property of their

respective owners.

1 NORD, Rare Disease Database, Primary Myelofibrosis, Accessed on 10/4/22,

https://rarediseases.org/rare-diseases/primary-myelofibrosis/

Logo: https://mma.prnewswire.com/media/652491/MENARINI_Group_Logo.jpg

SOURCE: Menarini Industrie Farmaceutiche Riunite