Document:

kpti-ex101_116.htm

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).

 

 

 

(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

 

	
 
	
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

 

			
	
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

 

		
	
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

 

 

(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

 

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]

 

ActiveUS 180642824Exhibit

Exhibit 10.1
[Jazz Pharmaceuticals Letterhead]
April 25, 2020
Kim Sablich 
[address on file]
Re:      Offer of employment with Jazz Pharmaceuticals
Dear Kim,
As discussed, I am very pleased to invite you to join Jazz Pharmaceuticals. This letter sets out the terms of your employment with Jazz Pharmaceuticals, Inc. (“Jazz Pharmaceuticals” or the “Company”).
1.Position, Duties and Responsibilities. Your initial assignment will be as Executive Vice President, General Manager North America (EVP, GM North America), reporting to me. This offer is for a full time position, based in Jazz Pharmaceuticals’ offices in Palo Alto, California. In this position, you will be a member of the Executive Committee. This position will require domestic and international business travel from time to time. As part of your employment relationship, you agree to comply with Jazz Pharmaceuticals’ policies and procedures in effect from time to time during your employment.
2.Base Salary, Annual Bonus, Signing Bonus. Your initial annual base salary rate will be $550,000, less all applicable deductions and withholdings and payable in accordance with Jazz Pharmaceuticals’ customary payroll practices. As an exempt employee, you will be paid on a salaried basis and you will be expected to work the number of hours required to do your job well and you are not eligible for overtime compensation. Salary is subject to periodic review and adjustment by Jazz Pharmaceuticals, in accordance with its normal practices; we have a Company- wide performance review process that takes place early in each calendar year.
You will be eligible for consideration of an annual bonus, and in this position, your annual target bonus will be 55%. The amount of your bonus will be based on the Company’s level of achievement of its annual objectives, and on your level of achievement of your objectives. Bonuses are not guaranteed, and whether there will be a bonus in any year, and the amount of any bonus, is within the discretion of the Board of Directors of Jazz Pharmaceuticals plc. Your bonus for 2020 will be prorated due to your partial year of employment.
In addition, Jazz Pharmaceuticals will pay you a signing bonus in the total amount of $300,000, less all applicable deductions and withholdings, paid to you in two equal installments. The first payment of $150,000 is payable on the first regular pay date occurring 30 days after your employment start date, and the second payment of $150,000 is payable on the first regular pay date occurring six (6) months after your employment start date, subject to your continued employment in good standing with Jazz Pharmaceuticals through each applicable date. You will be required to repay the signing bonus in full if you resign from your employment with Jazz Pharmaceuticals

April 25, 2020
Kim Sablich
within one year of your employment start date; in such case, you will be expected to repay the full amount of the signing bonus on your last day of employment or within 30 days thereafter.
3.Employee Benefits. You generally will be eligible to participate in all employee benefits which are extended to other similarly-situated employees at Jazz Pharmaceuticals, including medical and dental benefits, life insurance and other benefits offered to regular employees, subject to the terms and conditions of the benefit plans. You will be eligible for paid time off and holidays in accordance with Jazz Pharmaceuticals’ policies, and you will be a participant in the Jazz Pharmaceuticals Amended and Restated Executive Change in Control and Severance Benefit Plan.
4.Equity Awards. Your offer includes a grant of options to purchase 42,000 Jazz Pharmaceuticals plc ordinary shares and a grant of 16,800 restricted stock units (“RSUs”) giving you a right to receive Jazz Pharmaceuticals plc ordinary shares at a future date, subject to approval by the Compensation Committee, the terms and conditions of the Jazz Pharmaceuticals plc 2011 Equity Incentive Plan, and the terms and conditions of the applicable award agreements, which will be provided to you as soon as practicable after the grant date. Subject to your continued employment on each vesting date, the options will vest 1/4th on the first annual anniversary of your start date and 1/48th of the total granted per month thereafter, and the RSUs will vest 1/4th annually over four years. The options will have an exercise price that equals the fair market value of Jazz Pharmaceuticals plc ordinary shares on the date of grant. The RSUs will have no exercise price. The options and RSUs will be granted on the second trading day following the filing date of the Company’s next quarterly or annual report filed with the U.S. Securities and Exchange Commission following your start date in accordance with the Company’s Equity Incentive Grant Policy.
5.Confidential Information and Inventions Agreement, Outside Employment. To enable Jazz Pharmaceuticals to safeguard its proprietary and confidential information, it is a condition of employment that you sign and comply with Jazz Pharmaceuticals’ standard form of “Employee Confidential Information and Inventions Agreement.” We understand that you are likely to have signed similar agreements with prior employers, and wish to impress upon you that Jazz Pharmaceuticals does not want to receive the confidential or proprietary information of others, and does not want you to use such information in the course of your employment with us, and Jazz Pharmaceuticals will support you in respecting your lawful obligations to prior employers. By accepting this offer, you are representing to Jazz Pharmaceuticals that your performance of your duties will not violate any agreements you may have with, or trade secrets of, any third parties. You agree that, during your employment with Jazz Pharmaceuticals, you will not engage in any business activity that competes with Jazz Pharmaceuticals, and you will notify your manager if you are considering accepting outside work, including self-employment, consulting arrangements, or any roles on any corporate Boards of Directors.
6.Code of Conduct. Jazz Pharmaceuticals is committed to integrity and the pursuit of excellence in all we do. We fulfill these commitments while upholding a high level of ethical conduct. The Code of Conduct is one element of Jazz Pharmaceuticals’ efforts to ensure lawful and ethical conduct by the Company and its subsidiaries and their employees, officers and directors. It is a condition of employment that you read, agree to and sign Jazz Pharmaceuticals’ Code of Conduct in the first week of employment.  If you have questions about the Code of 

April 25, 2020
Kim Sablich
Conduct, please let Human Resources know and we will ensure that you receive answers to your inquiries as quickly as possible.
7.At-Will Employment Status. Should you decide to accept our offer, you will be an “at-will” employee of Jazz Pharmaceuticals. This means that either you or Jazz Pharmaceuticals may terminate the employment relationship at any time, with or without cause, and with or without advance notice. Due to your at-will employment status, Jazz Pharmaceuticals also retains the discretion to modify the terms and conditions of your employment, including but not limited to your salary, incentive compensation and benefits, as well as your job title, location, duties, responsibilities, assignments and reporting relationships. Participation in any benefit, compensation or bonus program does not change the nature of the employment relationship, which remains “at-will”. Your at-will employment status can only be changed in a writing signed by you and the Chief Executive Officer of Jazz Pharmaceuticals.
8.Authorization To Work. Federal government regulations require that all employees present documentation verifying their identity and demonstrating that they are authorized to work in the United States. Your employment is contingent on your ability to prove your identity and authorization to work in the United States, and your compliance with the government’s employment verification requirements.
9.Offer Contingencies. This offer is contingent upon satisfactory completion (as determined by the Company) of your background and reference checks, including but not limited to verification of previous employment record, academic achievement and criminal background. Accordingly, we strongly suggest that you not resign from your current employment or make any other arrangements that you would not otherwise make until we advise you that the background and reference checks have been completed to our satisfaction.
10.Complete Offer and Agreement. This letter, including the Employee Confidential Information and Inventions Agreement referenced herein, contains our complete understanding and agreement regarding the terms of your employment with Jazz Pharmaceuticals, and it is entered into without reliance on any promise or representation, written or oral, other than those expressly contained herein, and it supersedes any other such promises, warranties or representations. There are no other, different or prior agreements or understandings on this or related subjects.
11.Start Date, Acceptance of Offer. Your start date will be mutually agreed between you and Jazz Pharmaceuticals. To accept our offer of employment, please sign the enclosed copy of this letter in the space indicated below, and then return the completed letter to me by the close of business on Friday, May 1, 2020. If we do not receive the fully signed letter back from you by this date, this offer of employment will terminate.

April 25, 2020
Kim Sablich
Kim, we are impressed by your accomplishments and potential, and we are enthusiastic at the prospect of you joining us. I look forward to your early acceptance of this offer, and to your contributions to the growth and success of Jazz Pharmaceuticals.
If you have any questions about this letter, please let me know or feel free to contact Heidi Manna, our Chief Human Resources Officer.
	
	
	Sincerely,

	/s/ Dan Swisher

	Daniel Swisher

	President & Chief Operating Officer

	
				
	ACCEPTANCE OF EMPLOYMENT OFFER:

	I hereby accept the offer of employment by Jazz Pharmaceuticals on the terms set forth in this letter:

	/s/ Kim Sablich
	 
	 

	Kim Sablich
	 
	 

	Date:
	     02-May-2020

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