PR93820

Karyopharm and Menarini Group Enter into Exclusive License Agreement to Commercialize NEXPOVIO (R) (selinexor) in Europe and Other Key Global Territories

NEWTON, Mass. and FLORENCE, Italy, Dec. 21, 2021 /PRNewswire=KYODO JBN/ --

- Menarini Group Obtains Exclusive Rights to Commercialize NEXPOVIO for the

Treatment of Hematologic and Solid Tumor Oncology Indications in Europe

(including the United Kingdom), Latin America and Other Key Countries

- Karyopharm to Receive $75 Million Upfront, then Eligible to Receive Up to

$202.5 Million in Future Milestones, Plus Tiered, Double-digit Royalties on Net

Sales

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 their entry into an exclusive licensing agreement whereby

Menarini will commercialize NEXPOVIO, Karyopharm's first-in-class, oral

Selective Inhibitor of Nuclear Export (SINE) compound, in Europe and other key

global territories.

Under the terms of the agreement, Menarini received exclusive rights to

commercialize NEXPOVIO for the treatment of oncology indications in the

European Union and other European countries (including the United Kingdom),

Latin America and other key countries. In exchange, Karyopharm will receive an

upfront payment of $75 million (USD) in 2021 and is eligible to receive up to

an additional $202.5 million in future milestones, plus tiered double-digit

royalties on net sales of NEXPOVIO in the licensed territories.  

"Menarini is a global pharmaceutical company, with a strong heritage and

footprint in Europe and an unwavering commitment to patients, that is dedicated

to innovation and bringing new treatment options in oncology.  Menarini is an

ideal partner to maximize selinexor's potential to have a positive impact on

the treatment of cancer in Europe, Latin America and other key countries and

this transaction marks an important step forward toward that goal," said

Richard Paulson, President and Chief Executive Officer of Karyopharm. "With a

shared vision on the potential of selinexor and Menarini's commercialization

expertise, this agreement aligns our two companies with the common goal of

expanding the number of patients who can access NEXPOVIO in these important

global territories."

"We are delighted to partner with Karyopharm to provide NEXPOVIO in Europe,

Latin America and other key countries in the world," said Elcin Barker Ergun,

Chief Executive Officer of the Menarini Group."Patients suffering from multiple

myeloma continuously need different options as resistance develops to first

line therapies and the unique mechanism of action of selinexor makes it an

ideal partner as a backbone therapy in second line and beyond. The potential

further expansion of NEXPOVIO in solid tumors, such as in endometrial cancers,

where limited options exist, underline the wide potential of selinexor in

playing a role in cancer treatments aligning well with our mission of providing

therapies that can prolong patient lives."    

NEXPOVIO has received conditional marketing authorization from the European

Commission 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. The European Medicines

Agency (EMA) has validated the Marketing Authorization Application (MAA) for

NEXPOVIO in combination with Velcade (R) (bortezomib) and low-dose

dexamethasone for the treatment of multiple myeloma following at least one

prior therapy. The MAA will be reviewed by the Committee for Medicinal Products

for Human Use (CHMP), which will issue an opinion to the European Commission

regarding the potential approval for the expanded indication. This review is

expected to be completed during the first half of 2022.

About NEXPOVIO (R) (selinexor)

NEXPOVIO, which is marketed as XPOVIO in the U.S., is a first-in-class, oral

Selective Inhibitor of Nuclear Export (SINE) compound. 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. NEXPOVIO (selinexor) has been granted conditional marketing

authorization by the European Commission 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.

Therapeutic indication for NEXPOVIO in the EU as well as The EEA Countries of

Iceland, Liechtenstein and Norway

NEXPOVIO is indicated 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.

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.

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.

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 (30%) of selinexor in combination with

dexamethasone were nausea, thrombocytopenia, fatigue, anaemia, decreased

appetite, decreased weight, diarrhoea, vomiting, hyponatraemia, neutropenia and

leukopenia.

The most commonly reported serious adverse reactions (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 authorization 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.

Please see NEXPOVIO Summary of Product Characteristics and European Public

Assessment Report at

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

About Karyopharm Therapeutics

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

pharmaceutical company pioneering novel cancer therapies and dedicated to the

discovery, development, and commercialization of first-in-class drugs directed

against nuclear export for the treatment of cancer and other 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 (R) (selinexor), is approved in the U.S. in

multiple hematologic malignancy indications, including in combination with

Velcade (R) (bortezomib) and dexamethasone for the treatment of adult patients

with multiple myeloma after at least one prior therapy, in combination with

dexamethasone for the treatment of adult patients with heavily pretreated

multiple myeloma and as a monotherapy for the treatment of adult patients with

relapsed or refractory diffuse large B-cell lymphoma. NEXPOVIO (R) (selinexor)

has also been granted conditional marketing authorization in combination with

dexamethasone for adult patients with heavily pretreated multiple myeloma by

the European Commission. 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.

About Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics

company, with a turnover of $4.2 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 10 Research and

Development centers, Menarini's products are available in 140 countries

worldwide.

Menarini has a deep commitment for developing treatments addressing oncological

and hematologic diseases. Menarini actively develops Elzonris (marketed in US

and Europe for BPDCN) for multiple hematologic malignancies, including AML, s

CMML and myelofibrosis, and elacestrant and felezenexor for solid tumor

indications. Additionally, the FDA recently granted MEN1703 an orphan drug

designation for AML. For further information, please visit www.menarini.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 the potential to receive milestone and

royalty payments under the license agreement with Menarini, the success of

Karyopharm's arrangement with Menarini and the parties' ability to work

effectively together, the timing of submissions to regulatory authorities,

Karyopharm's expectations and plans relating to XPOVIO for the treatment of

hematologic malignancies or certain solid tumors; the expected design of the

Company's clinical trials; and the therapeutic potential of and potential

clinical development plans for Karyopharm's drug candidates, especially

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 any of Karyopharm's

drug candidates, including selinexor, 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 ability of Karyopharm or

Menarini to fully perform their respective obligations under the license

agreement; 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 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 obtain and

maintain requisite regulatory approvals and 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 September 30,

2021, which was filed with the Securities and Exchange Commission (SEC) on

November 3, 2021, 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 press release are

the property of their respective owners.

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Source: Menarini Industrie Farmaceutiche Riunite