EXHIBIT10.1

Certain identified information has been excluded from the exhibit because it is
both (i) not material and (ii) would likely cause competitive harm to the
Company, if publicly disclosed.  

Double asterisks denote omissions.

AMENDMENT TO LICENSE AGREEMENT

This Amendment to License Agreement (this “Amendment”) is entered into as of May
1, 2020 (the “Amendment Date”), by and among Karyopharm Therapeutics Inc., a
Delaware corporation (“Karyopharm”), and Antengene Therapeutics Limited, a
corporation organized and existing under the laws of Hong Kong
(“Antengene”).  Capitalized terms used herein and not defined herein shall have
the meanings ascribed to them in the Agreement (as defined below).

WHEREAS, Karyopharm and Antengene entered into that certain License Agreement,
dated as of May 23, 2018 (the “Agreement”), pursuant to which Antengene obtained
exclusive rights to Develop and Commercialize Licensed Compounds in the Field in
the Antengene Territory;

WHEREAS, the Parties desire to amend the Agreement to expand the Antengene
Territory and modify other rights and obligations of the Parties as set forth
below;

NOW, THEREFORE, in consideration of the premises and mutual covenants contained
herein, the Parties hereby agree to modify the Agreement as follows:

 

1.

Amendments Relating to Expansion of the Antengene Territory.

(a)As of the Amendment Date, the definition of “Antengene Territory” in Section
1.8 of the Agreement is deleted in its entirety and replaced with the following:

“Antengene Territory” means the following countries and territories: Mainland
China, Taiwan, Hong Kong, Macau, South Korea, Brunei, Cambodia, Indonesia, Laos,
Malaysia, Myanmar, Philippines, Singapore, Thailand, Vietnam, Australia and New
Zealand.

(b)As of the Amendment Date, the definition of “Karyopharm Territory” in Section
1.48 of the Agreement is deleted in its entirety and replaced with the
following:

“Karyopharm Territory” means all countries and territories of the world other
than the Antengene Territory.

(c)As of the Amendment Date, the definition of the “Ono Territory” in Section
1.63 of the Agreement is deleted and replaced with “Reserved.”.

(d)As of the Amendment Date, the definition of “Business Day” in Section 1.10 of
the Agreement is deleted in its entirety and replaced with the following:

“Business Day” means any day other than a day which is a Saturday, a Sunday, any
day banks are authorized or required to be closed in  the  Boston,
Massachusetts, United  States or Shanghai, China or Melbourne, Australia or any
day within Karyopharm’s corporate holidays (for Karyopharm’s obligations) or
Antengene’s corporate holidays (for Antengene’s obligations).

 

 

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(e)As of the Amendment Date, a definition of “Indication” is added to the
Agreement as a new Section 1.84 as the following:

“Indication” means, with respect to a particular drug, a sign, a symptom or a
medical condition which makes the use of that drug for treatment advisable. In
respect of cancer, different forms of cancer (e.g. skin cancer or lung cancer)
and different cancer subtypes for which it is necessary to undertake separate
Clinical Trials (not including Phase I Clinical Trials) to obtain Regulatory
Approval for a Licensed Product for such form or subtype of cancer shall also be
considered separate Indications for this Agreement, however, provided that a
form or subtype of cancer of a different genotype within the same form or
subtype of cancer shall be considered a same Indication.  However, different
lines of treatment for the same cancer subtype (for example, first line
treatment and second line treatment of small cell lung cancer) and different/new
combinations shall not be considered separate Indications.

(f)As of the Amendment Date, the definition of “Field” in Section 1.10 of the
Agreement is deleted in its entirety and replaced with the following:

“Field” means for Selinexor, Eltanexor, and KPT-9274: the diagnosis, treatment
and/or prevention of cancer in humans; and for Verdinexor: the diagnosis,
treatment and/or prevention of all indications in humans excluding cancer,
precancer, malignant and benign tumors, and other proliferative or neoplastic
disorders and except for the indications as listed on Schedule 1.28, however,
provided, that, subject to Section 8.12, the Field of Verdinexor shall be
extended to the diagnosis, treatment and/or prevention of cancer in humans in
Antengene Territory, if Karyopharm initiates clinical development of Verdinexor
or licenses any Third Party to Develop Verdinexor for the diagnosis, treatment
and/or prevention of cancer in humans in any territory.

(g)As of the Amendment Date, the Section 7.4 of the Agreement is deleted in its
entirety and replaced with the following:

Prior to making a licensing proposal relating to any pharmaceutical product that
inhibits any of XPO1, NAMPT and PAK4 (“New Product”) to any Third Party in the
Antengene Territory, Karyopharm shall provide Antengene a report to evaluate the
New Product (collectively, “New Product Proposal”).  Antengene shall provide
Karyopharm a written notice indicating whether Antengene would like to develop
such New Product within [**] after receiving the New Product Proposal (the
“Evaluation Period”).  Karyopharm shall not engage in developing or
commercializing the New Product in humans within the Territory (including but
not limited to negotiation with any Third Party regarding the New Product)
unless Antengene fails to accept the New Product Proposal within the Evaluation
Period.

2

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2.

Amendment Relating to License Grants to Karyopharm. As of the Effective Date of
the Agreement, Section 7.1.2 of the Agreement is deleted in its entirety and
replaced with the following:

License Grants to Karyopharm.  Antengene hereby grants Karyopharm a
non-transferable (except as provided in Section 14.1), sublicenseable (including
through multiple tiers) (subject to Section 7.2), royalty-free license under
Antengene Technology to Develop, Manufacture, have Manufactured, use and
Commercialize Licensed Compounds and Licensed Products in the Field in the
Karyopharm Territory, such license to be (a) exclusive (even as to Antengene and
its Affiliates) with respect to (i) Antengene Technology and (ii) Antengene’s
interest in Joint IP, in each case ((i) and (ii)) that is generated or acquired
after the Effective Date in connection with Development, Manufacturing or
Commercialization activities with respect to Licensed Products by or on behalf
of Antengene or any of its Related Parties and (b) non-exclusive with respect to
all other Antengene Technology and Joint IP.  

 

3.

Amendments to Termination provisions.

(a)As of the Effective Date of the Agreement, Section 13.4.1(c) of the Agreement
is deleted in its entirety and replaced with the following:

The license grants to Karyopharm in Section 7.1.2 shall survive and be expanded
to include the Antengene Territory.

(b)As of the Effective Date of the Agreement, Section 13.4.2(b) of the Agreement
is deleted in its entirety and replaced with the following:

the license grants to Antengene shall terminate, and the license grants to
Karyopharm in Section 7.1.2 shall survive and be expanded to include the
Antengene Territory;

 

4.

Amendments Relating to Financial Terms.

(a) In consideration for this Amendment, Antengene shall pay Karyopharm a
one-time, non-refundable, non-creditable upfront payment of Twelve Million (12
Million) US Dollars as soon as is practicable but in no event later than [**]
after the Amendment Date and receipt of invoice by Antengene.

(b)As of the Amendment Date, Section 8.2.1 of the Agreement is amended to add
the following Milestone Payments to the chart contained in Section 8.2.1 of the
Agreement, in addition to the Milestone Payments presently listed therein:

 

Development Milestone Event

Development Milestone Payment (in USD)

3

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Development Milestone Event

Development Milestone Payment (in USD)

Development / Regulatory Milestones -

Selinexor

[**]

[**]

[**]

[**]

 

For purposes of this revised Section 8.2.1, [**] means the [**].

(c)As of the Amendment Date, the development/regulatory milestones-KPT-9274 and
the development/regulatory milestones-Verdinexor in Section 8.2.1 of the
Agreement is deleted in its entirety and replaced with the following:

 

Development / Regulatory Milestones – KPT-9274

[**]

[**]

[**]

[**]

[**]

[**]

 

 

 

Development / Regulatory Milestones – Verdinexor

[**]

[**]

[**]

[**]

[**]

[**]

 

(d)As of the Amendment Date, the table contained in Section 8.4.1 of the
Agreement is deleted in its entirety and replaced with the following table:

 

Royalty Rate - Selinexor

 

Tiered: [**] of Annual Net Sales of the Product in Mainland China and Macau
(tiers in USD):

•   [**]

•    [**]

•    [**]

•    [**]

•    [**]

Tiered: [**] of Annual Net Sales of the Product in the Antengene Territory,
excluding Mainland China and Macau (tiers in USD):

•    [**]

•    [**]

•    [**]

•    [**]

 

4

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Royalty Rate - Eltanexor

Tiered: [**] of Annual Net Sales of the Product in the Antengene Territory
(tiers in USD):

•    [**]

•    [**]

•    [**]

•    [**]

•    [**]

Royalty Rate - KPT-9274

Tiered: [**] of Annual Net Sales of the Product in the Antengene Territory,
(tiers in USD):

•    [**]

•    [**]

•    [**]

•    [**]

•    [**]

Royalty Rate - Verdinexor

Tiered: [**] of Annual Net Sales of the Product in the Antengene Territory,
(tiers in USD):

•    [**]

•    [**]

•    [**]

•    [**]

•    [**]

5

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(e)As of the Amendment Date, the Section 8.4.2 of the Agreement is deleted in
its entirety and replaced with the following:

Royalty Reduction by Entry of Generic Version and Expiration of Patent Rights.
If at any time during the Royalty Term, (i) any Third Party (other than a
Sublicensee) makes all Generic Versions (defined below) of such Licensed Product
commercially available in such country in the Antengene Territory and the
Generic Version(s) constitute more than [**]% of the sales volume in the
country, or (ii) in Mainland China or Australia or South Korea, all Karyopharm
Patent Rights whose Valid Claim Covers such Licensed Product in Mainland China
or Australia or South Korea expire, provided, however, that the expiration of
Karyopharm Patent Rights is not caused, directly or indirectly, by any act or
omission by or on behalf of Antengene or its Affiliates, [**] then the royalty
rate applicable to Net Sales of such Licensed Product in such country shall be
reduced to [**] percent ([**]%).  “Generic Version” means a product that: (a)
contains as an active pharmaceutical ingredient a chemical composition that is
assigned the same INN (international nonproprietary name) as is assigned to
active pharmaceutical ingredient contained in the corresponding Licensed Product
being marketed in the Antengene Territory; (b) obtained marketing approval in a
country in the Antengene Territory by means of an abridged procedure that relies
(i) in whole or in part on the safety and efficacy data contained in the NDA for
such Licensed Product submitted by Antengene in such country, and (ii) on
establishing bioequivalence to the Licensed Product; and (c) has been granted
marketing approval in the Antengene Territory and is marketed by an entity other
than Antengene, its Affiliates or its Sublicensees.  

 

5.

Continued Effectiveness of Agreement.  All other terms and conditions in the
Agreement that are not hereby amended are to remain in full force and effect.

 

6.

Counterparts. This Amendment may be executed in two (2) or more counterparts,
including by facsimile or PDF signature pages, each of which shall be deemed an
original, but all of which together shall constitute one and the same
instrument.

[Signature Pages Follow]

 

6

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IN WITNESS WHEREOF, and intending to be legally bound hereby, the Parties have
caused this Amendment to be executed by their respective duly authorized
officers as of the date first written above.

 

Antengene Therapeutics Limited

 

KARYOPHARM THERAPEUTICS INC.

 

 

 

BY:

/s/ Jay Mei

 

BY:

Christopher B. Primiano

 

 

 

 

 

NAME:

Jay Mei

 

NAME:

Christopher B. Primiano

 

 

 

 

 

TITLE:

CEO

 

TITLE:

SVP, Chief Business Officer

 

 

 

 

 

April 29, 2020

 

May 1, 2020

 

 

[Signature Page to First Amendment to License Agreement]

 

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