AGREEMENT TO DEVELOP, SUPPLY AND MARKET ATG-FRESENIUS NORTH AMERICA

Exhibit 10.1

[*****] A CONFIDENTIAL PORTION OF THE MATERIAL HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION .

FRESENIUS BIOTECH GmbH

AND

NABI BIOPHARMACEUTICALS

AGREEMENT TO

DEVELOP, SUPPLY AND MARKET ATG – FRESENIUS NORTH AMERICA

March 30, 2006

 

- i -

 

- ii -

 

- iii -

FRESENIUS BIOTECH GmbH

AND

NABI BIOPHARMACEUTICALS

AGREEMENT TO

DEVELOP, SUPPLY AND MARKET ATG – FRESENIUS NORTH AMERICA

This AGREEMENT TO DEVELOP, SUPPLY AND MARKET ATG – FRESENIUS NORTH AMERICA is made as of the 30th day of March 2006, by and between FRESENIUS BIOTECH GmbH , a company organized under the laws of the Federal Republic of Germany having a principal place of business at Else-Kröner-Straße 1, 61352 Bad Homburg, Germany, hereinafter referred to as “ FRESENIUS ” and NABI BIOPHARMACEUTICALS , a corporation organized under the laws of Delaware having a principal place of business at 5800 Park of Commerce Blvd. N.W., Boca Raton, Florida 33487 USA, hereinafter referred to as “ NABI ”.

RECITALS

WHEREAS, FRESENIUS has developed a product which it refers to as ATG-FRESENIUS NORTH AMERICA, an immunosuppressive polyclonal antibody product which has the initial specifications set forth on Schedule A and is sometimes commonly referred to as EZ 2053 (“ ATG ”);

WHEREAS, a product similar to, but which is the global version of, ATG (“ Global ATG ”) is approved and marketed in 50 countries for multiple indications, but has not been approved for marketing in the United States or Canada;

WHEREAS, FRESENIUS can supply ATG from its manufacturing site in Germany that has been approved by the relevant German regulatory authority (the “ Facility ”) and the human adsorption materials are sourced in compliance with the current requirements of the US Food and Drug Administration;

WHEREAS, FRESENIUS had previously authorized Enzon Pharmaceuticals Inc. (“ Enzon ”) to conduct phase II and III studies of ATG, but such relationship has been terminated by mutual agreement of both parties;

WHEREAS, FRESENIUS has the right to authorize a third party to conduct phase II and III studies of ATG under an Investigational New Drug application filed with the US Food and Drug Administration and relevant Canadian authorities for solid organ transplants ( “SOTs” ), including approved protocols for use in conjunction with renal and lung transplants, as well as to provide such third party with all rights to data and other filings with the US Food and Drug Administration and certain rights under agreements with respect thereto with the relevant clinical research organizations, investigators, institutions, ethics board approvals, and the like;

WHEREAS, the parties intend that this Agreement will encompass, and the term Licensed Product (as defined below) will extend to, the use of ATG with respect to supplemental and additional indications (including stem cell transplants ( “SCTs ”)) subject to, and upon compliance with, appropriate clinical procedures and studies and regulatory approvals which may be undertaken in accordance with the rights granted to each of the parties in this Agreement with respect thereto;

WHEREAS, FRESENIUS has rights to certain know-how, clinical data and right to reference certain filings with the US Food and Drug Administration regarding ATG;

WHEREAS, FRESENIUS has the ability to supply a third party with ATG to conclude the clinical studies necessary to complete a Biologics License Application to be filed with the US Food and Drug Administration, and any corresponding applications which would need to be filed with the Canadian authorities before ATG can be marketed in Canada; and

WHEREAS, NABI wishes to complete the necessary clinical studies, to submit a Biologics License Application to market the Licensed Product in the US and a New Drug Submission to market the Licensed Product in Canada, in each case after approval;

NOW THEREFORE, in consideration of the mutual covenants set forth below, the parties agree as follows:

AGREEMENT

1. DEFINITIONS/INTERPRETATION

1.1. DEFINITIONS

In addition to definitions set forth throughout this Agreement, the following capitalized terms shall have the meanings ascribed to them below:

A. “ Affiliate(s) ” means, with respect to any specified Person, any other Person that, directly or indirectly, through one or more intermediaries, is in Control of, is Controlled by, or is under common Control with, such specified Person. For purposes of this definition, “ control ” (including with its correlative meanings, the terms “controlled by” and “under common control with”), as used with respect to any Person, shall mean the possession, directly or indirectly, of the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of voting securities or by contract or otherwise.

B. “ BLA ” means a Biologics License Application filed with the US FDA.

C. “ Business Day ” means a day which is a normal day of business in Bad Homburg, Germany or the next business day if such day falls on a Saturday, Sunday, or legal holiday in Bad Homburg, Germany,

D. “ Certificate of Analysis ” means a report as is customary in the industry and fully compliant with regulatory and legal requirements, including those

 

- 2 -

specifying lot release protocols, certifying as to the following with respect to each batch of Licensed Product Delivered hereunder: that the source of its constituents, the manufacturing process to produce it and the finished package product itself comply with the BLA (including the Specficiations) , the Technical Sections and all current applicable US FDA regulations, including GMP, and other applicable regulatory requirements.

E. “ CMC ” means chemistry, manufacturing and controls information.

F. “ Competitive Product ” means [*****].

G. “ Confidential Information ” means any information of either party or of any of their Affiliates which is not generally known, the continued secrecy of which information provides the possessor of this information with some economic advantage, and which the possessor of this information has taken reasonable steps under the circumstances to keep secret.

H. “ CRO ” means a clinical research organization.

I. “ Delivery ” is defined in Section 7.6.

J. “ Effective Date ” means the date first above written.

K. “ First Commercial Sal e” means, with respect to Licensed Product, the first sale by NABI for end use or consumption of the Licensed Product in the Territory after all approvals, including marketing and pricing approvals, if any, have been granted by the US FDA and any other applicable regulatory authority.

L. “ FRESENIUS ATG Trademarks ” is defined in Section 8.1.

M. “ FRESENIUS Scheduled Obligation s” is defined in Section 4.1(B).

N. “ GCP ” means the current good clinical practices regulations of the US FDA.

O. “ GMP ” means current good manufacturing practices as established from time-to-time by the US FDA and as otherwise applicable to products to be marketed in the Territory. If at any time US or Canadian guidelines specifying good manufacturing practices are not applicable to the manufacture of the Licensed Product to be distributed in such country, then the applicable European Pharmacopoeia shall apply.

P. “ Improvements ” means any modification or change, whether or not any such modification or change is patentable, to ATG or to Global ATG that can be used in connection with ATG, including: (i) any composition which includes ATG or such Global ATG; (ii) any substitute for ATG or such Global ATG that is based on or utilizes ATG or such Global ATG; and (iii) any process for making or using ATG or such Global ATG, or any composition which includes, or is a substitute for, ATG or such Global ATG as described above.

 

- 3 -

Q. “ IND ” means an Investigational New Drug application filed with the US FDA.

R. “ Inflation Factor ” means the increase in inflation for a specified period as determined in accordance with the non-adjusted Index der Erzeugerpreise gewerblicher Produkte from the Deutsches Statistisches Bundesamt.

S. “ Intellectual Property Rights ” means a party’s (i) patents and patent applications that claim a composition including, or a method of using, Licensed Product; (ii) Know-How and trade secrets concerning the manufacture, processing, marketing, distribution, or pricing of Licensed Product; (iii) FRESENIUS ATG Trademarks used in conjunction with Licensed Product; (iv) copyrights in works used in conjunction with the manufacturing, processing, marketing, distribution or pricing of Licensed Product; (v) rights to use and rely upon any clinical data concerning Licensed Product; and (vi) the right to reference any filing with a governmental regulatory authority for approval to market Licensed Product.

T. “ Know-How ” means all know-how relating to the Licensed Product including clinical data, manufacturing data, and test and measurement data, but only to the extent that such know-how and any data included therein is used or useful in, or necessary for, marketing of ATG or is necessary for a party to comply with its obligations under this Agreement.

U. “ Licensed Product ” means ATG and all Improvements thereto that are either owned or controlled with the right to sublicense in the Territory by FRESENIUS at any time during the term of this Agreement.

V. “ NABI’s Average Quarterly Commercial Price” means, with respect to each quarter, the amount equal to NABI’s Net Retail Sales for such quarter divided by the number of [*****] vials of Licensed Product sold under the invoices evidencing such sales.

W. “NABI’s Cumulative Annual Net Retail Sales” means the sum of all of NABI’s actual Net Retail Sales of Licensed Product from the beginning of a calendar year through the measurement date.

X. “ NABI’s Scheduled Obligations ” is defined in Section 4.1(B).

Y. “ NABI Trademarks ” means the registered trademarks of NABI used in connection with the marketing, promotion, distribution and sale of Licensed Products in the Territory.

Z. “ Net Retail Sales ” means the gross invoice amount billed with respect to Licensed Products by NABI to its customers, exclusive of NABI’s sublicensees, and by NABI’s sublicensees to their customers, in each case less the following items:

 

- 4 -

taxes; shipping charges; and credits for pricing adjustments, any bona fide returns (net of all returns actually made), charge backs, rebates and discounts; provided, however, that NABI shall not (directly or indirectly) allow the Licensed Product to be sold (or offered for sale) in combination with other products resulting in a disproportionate credit, discount or rebate to be applied to the Licensed Product.

AA. “ Reviewable BLA ” means a BLA that is complete in all formal aspects.

BB. “ Steering Committee ” is defined in Section 4.6.

CC. “ Technical Sections ” shall have the meaning provided by 21 C.F.R. §600 et. seq.

DD. “ Termination Date ” means the last day of the term of this Agreement as set forth in Section 11.1 or such earlier date as either party shall cause this Agreement to be terminated as provided in Section 11.2.

EE. “ Territory ” means the United States (including its territories or possessions) and Canada.

FF. “ Transfer Price ” is defined in Section 7.3.

GG. “ US FDA ” means the US Food and Drug Administration as defined above, or any successor agency.

1.2. I NTERPRETATION .

The parties have participated jointly in the negotiation and drafting of this Agreement. In the event an ambiguity or question of intent or interpretation arises, this Agreement shall be construed as if drafted jointly by the parties and no presumption of burden of proof shall arise favoring or disfavoring any party by virtue of the authorship of any of the provisions of this Agreement. References in this Agreement to any gender include references to all genders, and references to the singular include references to the plural and vice versa. The words “include”, “includes” and “including” when used in this Agreement shall be deemed to be followed by the phrase “without limitation”. Unless the context otherwise requires, references in this Agreement to Articles, Sections, Exhibits, Schedules, Appendices and Attachments shall be deemed references to Articles and Sections of, and Exhibits, Schedules, Appendices and Attachments to, such Agreement. Unless the context otherwise requires, the words “hereof’”, “hereby” and “herein” and words of similar meaning when used in this Agreement refer to this Agreement in its entirety and not to any particular Article, Section or provision of this Agreement.

2. GRANT OF RIGHTS

2.1. By FRESENIUS

For valuable consideration, and subject to the terms and conditions of this Agreement, FRESENIUS grants to NABI and NABI hereby accepts from FRESENIUS, the exclusive right

 

- 5 -

and license, in the Territory under any and all Intellectual Property Rights that FRESENIUS either owns or controls and has a right to sublicense with respect to the Licensed Product, (i) to perform research with respect to and to develop the Licensed Product and, (ii) to use, apply for approval, market, import for use or sale, offer for sale, and sell for all human uses/indications (but not manufacture or to have manufactured) the Licensed Product, together with, in each case, the right to sublicense.

2.2. By NABI

NABI grants to FRESENIUS a royalty-free, milestone-free, perpetual license to make, use, sell, offer for sale each Improvement that is either owned, or controlled with the right to sublicense, by NABI at any time during the term of this Agreement.

3. SPECIFIC OBLIGATIONS

3.1. Marketing

NABI shall use commercially reasonable efforts to market the Licensed Product in the Territory, after all necessary approvals have been obtained.

3.2. Sole Supply

FRESENIUS shall be NABI’s sole supplier of Licensed Product in the Territory, and NABI shall not order or purchase Licensed Product from any other party, or sell any Licensed Product which is procured from any other party, nor shall NABI manufacture (or cause to be manufactured) Licensed Product.

3.3. Export

During the term of this Agreement, NABI shall not export Licensed Product outside the Territory except that NABI shall have the right to fill orders of the US Department of Defense for its purposes outside the Territory.

3.4. Competition

A. Neither NABI nor any of its Affiliates shall, without the prior written consent of FRESENIUS (which may be granted or denied in the sole discretion of FRESENIUS)

(i) market, sell, manufacture for commercial sale or distribute in the Territory any Competitive Product, provided that, (x) the marketing, sale, manufacture for commercial sale and distribution of Competitive Products by NABI pursuant to Sections 3.4(B) or under circumstances to which Sections 14.4(A)(vi) or 14.4(B) apply shall not constitute a default under this Section 3.4 and (y) if NABI or any of its Affiliates has developed a Competitive Product (without violating their respective confidentiality obligations under this Agreement), NABI or its Affiliates may assign their rights (by sale or exclusive license for a

 

- 6 -

term which shall not be less than the remaining portion of the Initial Term (as defined in Section 11.1) plus five (5) years) in such Competitive Product to a third party (it being understood that neither NABI nor any of its Affiliates shall have any right of ownership or participation in such third party or the income or profit of such third party at any time other than through a royalty in connection with the license) and such action shall not constitute a breach of this Agreement for so long as NABI and its Affiliates do not engage in providing any direct or indirect marketing activity, or provide marketing direction or assistance, information or data in relation to such Competitive Product; or

(ii) acquire (by purchase, license or otherwise) rights in the Territory to market, sell or distribute any Competitive Product other than under the circumstances described in Sections 3.4(B), 14.4(A)(vi) or 14.4(B).

B. If NABI or any of its Affiliates shall determine to acquire, in the Territory, a group of products (whether directly through an acquisition of assets or indirectly through an acquisition of capital stock) and such acquisition includes (as a part of the entirety of the package) the right to sell, market or distribute a Competitive Product in the Territory in circumstances which do not involve a Change of Control (as defined in Section 14.4(B)(iv) below), NABI shall give FRESENIUS as much advance written notice of such intention as is reasonably feasible under the circumstances, as well as written notice of the consummation of such acquisition. If such written notice specifies that the Competitive Product will be acquired, then the notice must specify whether NABI intends to divest its interest in such product following its acquisition thereof. During the ninety (90) days following such notice, the parties will attempt to establish acceptable terms under which they would co-promote the Licensed Product in the Territory for the remaining term of this Agreement. Alternatively, the parties could agree upon another commercial relationship. If the parties are unable to agree upon acceptable terms regarding the ownership and exploitation of the Competitive Product in the circumstances described in this Section 3.4(b), if NABI’s rights to such Competitive Product in the Territory are not divested by NABI, or if such Competitive Product is not withdrawn from the market in the Territory, within twelve (12) months of its acquisition, then FRESENIUS will have the option at its discretion to terminate this Agreement pursuant to Section 11.2(A) below and reacquire all the rights to the Licensed Product in the Territory. In the event FRESENIUS decides to reacquire all the marketing rights to the Licensed Product, FRESENIUS will give written notice to NABI to implement the process of determining the Value of the Licensed Product in accordance with Section 14.4(B)(iii). FRESENIUS will have the option at its discretion to purchase the Licensed Product by giving written notice to NABI, within thirty (30) days after the determination of the Value, and paying to NABI an amount of cash equal to [*****] of the Value of the Licensed Product (as defined in and determined in accordance with the provisions of Section 14.4(B)(iii) below) at the time of its reacquisition.

 

- 7 -

3.5. Transition

A. FRESENIUS will deliver or cause Enzon to deliver to NABI within ninety (90) days of the date hereof, the IND for the Licensed Product and all the clinical data for ATG which is in the possession or control of Enzon. If FRESENIUS shall fail to deliver such IND and clinical data for ATG within ninety (90) days hereafter, FRESENIUS shall promptly reimburse to NABI the milestone payment referred to in Section 7.8(A)(i) and NABI shall have the right to terminate this Agreement.

B. Promptly following the date hereof, NABI shall use commercially reasonable efforts to cooperate with Enzon and FRESENIUS in connection with the transition from Enzon to NABI of responsibility for the current study and program for ATG which had been conducted by FRESENIUS and/or Enzon with respect to the Territory. As between FRESENIUS and NABI, FRESENIUS shall be liable for, and shall pay, (i) all costs and expenses which have accrued in connection with Enzon’s prior agreement with FRESENIUS for such ATG study and program as well as the costs directly associated with the transition thereof and (ii) if NABI proposes to conduct all or any portion of such study and program itself or through contract research organizations different from those presently engaged, FRESENIUS shall pay the costs owed to such contract research organizations as termination fees or damages for early termination, if any are owed.

C. Within [*****] of the Effective Date, FRESENIUS will send Enzon a letter requesting that Enzon immediately transfer the IND for the Licensed Product to NABI.

4. DEVELOPMENT

4.1. Development Plan

A. Within [*****] after the Effective Date (and taking into consideration the requirement of completing the task set forth in this Section 4.1(A) in order that the parties may comply with the obligations set forth in Section 4.1(B)), NABI will perform a CMC audit of the Facility and provide FRESENIUS with a detailed list of all items that NABI reasonably believes will need to be addressed and remedied in connection with the Facility before the first day of the second full calendar quarter prior to the planned submission to the US FDA of a Reviewable BLA in order that the Facility will be approved by the US FDA for the production of Licensed Product for marketing and distribution in the USA. The parties will negotiate the reasonableness, content and timing of the items specified by NABI during the thirty (30) days after delivery of the list to FRESENIUS. If the parties come to mutual agreement, then the items and time frames will be incorporated into and become part of the FRESENIUS Scheduled Obligations contemplated by Section 4.1(B) below. Failing such agreement each party will, upon the request of the other party, appoint an independent credentialed examiner or inspector familiar with FDA requirements for manufacturing facilities and request such appointed persons to designate a third

 

- 8 -

person who will act as the arbiter (the “ Arbiter ”). The Arbiter will be asked to resolve the differences between the parties and establish a definitive list of items to be remedied in the Facility in order that the same may comply with FDA requirements as then in existence for a manufacturing facility which will be examined in connection with a Reviewable BLA. Such determination will be final and binding on the parties and the cost for the services of the Arbiter shall be shared equally between the parties. FRESENIUS shall make such upgrades to the Facility as agreed by the parties or fixed by the Arbiter and as may be subsequently required by the US FDA during the term of this Agreement in order that the Facility will be, and will remain, approved by the US FDA for the production of Licensed Product for marketing and distribution in the USA.

B. Within [*****] after FRESENIUS delivers to NABI all of the clinical data required to be delivered pursuant to section 3.5(A), NABI shall meet with appropriate officials of the US FDA and determine the most efficient means of completing the studies which are necessary to commercialize the Licensed Product. Within sixty (60) days after the meeting with the US FDA, representatives of FRESENIUS and NABI shall meet with the Steering Committee and describe and discuss NABI’s strategy for development (clinical and regulatory) and commercialization of the Licensed Product in the Territory. The parties shall discuss in good faith the registration strategy and clinical studies that shall be undertaken to obtain marketing authorization in the Territory (starting with the U.S.) and establish specific milestones for: (i) the actions to be taken by NABI in order to assure efficient and expeditious approval of the Licensed Product for commercial sale in the U.S. and a time table for the realization thereof (collectively, “ NABI’s Scheduled Obligations ”); and (ii) based on the time table developed by the parties for the performance of various items necessary to obtain approval of the Licensed Product and depending on the time line for NABI to reasonably comply with NABI’s obligations, (x) the actions to be taken by FRESENIUS to upgrade the Facility to comply with the applicable US FDA manufacturing standards and the time table for the completion thereof as provided by Section 4.1(A) above; and (y) the date by which FRESENIUS will deliver to NABI whatever non-clinical (including toxicology and pharmacology (animal data)) package is required by the US FDA, which date may not be later than the first day of the second full calendar quarter prior to the planned submission to the US FDA of a Reviewable BLA (collectively the “ FRESENIUS Scheduled Obligations ”). Upon agreement and approval by the Steering Committee, the actions comprising and the time lines for completing the NABI Scheduled Obligations and the FRESENIUS Scheduled Obligations shall be a part of this Agreement as if set forth herein. The registration strategy shall include continuation of the lung transplant study currently underway and shall, at the option of NABI, specify whether the clinical studies for the SOT indication and the SCT indication shall be undertaken sequentially or contemporaneously in light of the estimated cost thereof and the mutual intention of the parties that the registration strategy shall be focused on minimizing the time to obtain necessary approvals in the Territory for the Licensed Product.

 

- 9 -

C. FRESENIUS shall use commercially reasonable means to deliver to NABI, within [*****] of the Effective Date, all the clinical data for ATG, and the clinical data for Global ATG that is relevant to NABI’s planned conduct of clinical studies and BLA submission to the US FDA and which, in either case, is in the possession or control of FRESENIUS (including the CRF and other pertinent files) together with such documents as may be necessary to reference any filing with the US FDA for approval of the Licensed Product as the same may exist on the Effective Date.

D. In the event of a disagreement between the parties with respect to the strategy or time table in the Territory, the NABI Scheduled Obligations, the FRESENIUS Scheduled Obligations or any supplemental agreement to be entered into regarding safety or quality, the parties shall first meet and confer and endeavor in good faith to resolve the disagreement. If the disagreement persists, the parties will elevate the discussion to the Steering Committee. If the Steering Committee cannot resolve the issue, the parties will elevate the discussion to their respective CEOs for resolution. If the disagreement cannot be resolved by the CEOs, NABI shall have the final deciding vote with respect thereto (except with respect to the Facility upgrade which is governed by Section 4.1(A), the content and date for delivery of the toxicology package which are governed by Section 4.1(B)(y) , any supplemental agreement to be entered into regarding quality, and the other FRESENIUS Scheduled Obligations).

E. NABI shall at all times during the development phase as well as during the commercialization process, give prompt written notice to FRESENIUS of any substantive, content-driven notices or communications (other than purely scheduling or administrative items) between NABI and regulatory agencies regarding the Licensed Product. Prior to any substantive, content-driven communications with the US FDA, the FRESENIUS members of the project team shall have reasonable notice of, and the opportunity to discuss, all matters in accordance with Section 4.6. NABI shall allow FRESENIUS the right, at its sole cost, to participate along with NABI in any meetings or conference calls with the US FDA and all other regulatory agencies, provided that NABI will have the final say in all matters to be communicated to the US FDA with respect to the Licensed Product.

F. FRESENIUS shall at all times during the development phase as well as during the commercialization process, give prompt written notice to NABI of any substantive, content-driven notices or communications between FRESENIUS and regulatory agencies regarding the safety and efficacy of Global ATG or the Licensed Product or the US FDA qualification of the Facility.

4.2. Clinical Development

A. NABI shall be responsible for the clinical development of the Licensed Product in the Territory and shall satisfy all costs associated with the conduct of clinical studies in connection with such development (except as set forth in Section 5.1).

 

- 10 -

B. After obtaining the first market authorization within the Territory for the Licensed Product, the parties will discuss the further conduct of global clinical studies to increase the utilization of the Licensed Product, both within and outside the Territory. Such collaboration may include sharing the design of future clinical studies to maximize global product usage, and sharing in the costs to undertake such studies.

C. Subject to compliance with any bona fide third party restrictions, each party will cooperate to make available and grant the other party the right to use, free of charge, such party’s data arising out of its clinical and non-clinical development of ATG or Global ATG, as the case may be, in its respective geographic areas of operation for the purpose of advancing the development and commercialization of the Licensed Product with respect to all indications..

D. The parties shall grant to each other such rights of reference to, and the right to re-submit, any regulatory approvals and dossiers held by them as are reasonably necessary or useful to assist the parties in obtaining regulatory approvals with respect to the Licensed Product in their respective geographic areas of operation.

4.3. Non-clinical, Including Toxicology, Pharmacology (Animal Data), CMC and Process Development

FRESENIUS has worldwide responsibility for the non-clinical development (including toxicology and pharmacology (animal data)), CMC and process development for the Licensed Product. FRESENIUS will provide all non-clinical (including toxicology and pharmacology (animal data)), CMC and process development information under the control of FRESENIUS as necessary for NABI to obtain and maintain regulatory approval of the Licensed Product in the Territory. The time table for the delivery of such information to NABI shall be as set forth in Section 4.1(C) and the FRESENIUS Scheduled Obligations. The parties agree to work together in good faith to attempt to increase the expiration dating for the Licensed Product. In the event that the parties are successful in extending the shelf life of the Licensed Product, the first three months of such extended period shall be for the benefit of NABI and the excess of such extended period (beyond the first three months) shall be split 2/3rds for the benefit of NABI and the balance shall be for the benefit of FRESENIUS.

4.4. Regulatory Approval of Licensed Product and Compliance

A. NABI will have responsibility for obtaining and maintaining regulatory approvals by the authorities in the Territory.

B. NABI shall hold and own any regulatory filings pertaining to Licensed Product in the Territory. NABI is not entitled to transfer any regulatory filings pertaining to Licensed Products in the Territory to third parties except as otherwise provided in this Agreement.

C. NABI shall be responsible for the conduct of regulatory product actions (including field corrections and recalls) and adverse event reporting in the Territory. NABI shall consult with FRESENIUS in advance and keep FRESENIUS

 

- 11 -

reasonably informed at all times as to any such contemplated or actual product actions. Notwithstanding that NABI shall be responsible to conduct all such regulatory product actions, the parties’ respective liability for the cost of all such regulatory product actions shall be determined in accordance with Section 10 of this Agreement.

D. FRESENIUS shall keep NABI reasonably and timely informed regarding any information relating to the Licensed Product in FRESENIUS’ possession that relates to product safety, efficacy, quality, or regulatory compliance regarding the Licensed Product.

E. Each party shall inform the other on a timely basis of any material regulatory issues in their respective territory and shall consult with the other party regarding same.

4.5. Development Costs

A. FRESENIUS shall bear the costs arising in connection with non-clinical, toxicology, CMC and process development information.

B. Aside from the costs for Licensed Product for investigational studies related to SOT and SCT (which are addressed in Section 5.1) NABI shall bear the costs for clinical development and regulatory approval of the Licensed Product for SOT, SCT and all other indications in the Territory.

4.6. STEERING COMMITTEE AND WORKING GROUP

A. The parties will establish a steering committee, which will supervise the development and commercialization of the Licensed Product and resolve any issues as they may arise (the “ Steering Committee ”). Furthermore, the parties will establish a project team, which shall be responsible for the project on a working level and report to the Steering Committee. Each party will be equally represented on the Steering Committee, project team and any working group established by the Steering Committee.

B. The Steering Committee shall be comprised of two (2) representatives of each party to be designated in writing within thirty (30) days of the Effective Date. Either party may designate substitute representatives upon advance written notice. The Steering Committee shall meet at least two (2) times per year or more often as is reasonably requested by either party. The meetings may either be by telephone, videoconference or in person; provided that if the meetings are in person the site of the meeting will alternate between the parties.

C. The Steering Committee shall fix the number of representatives of the project team and any additional working group, provided each party shall have an equal number. Each party shall nominate its own Steering Committee, project team and working group representatives. In the event the project teams or working groups have disagreements, they shall be referred to the Steering Committee which shall resolve such disagreements as provided in Section 4.1(D) above.

 

- 12 -

5. MANUFACTURE AND SUPPLY

5.1. Clinical Development Supplies

In connection with the development of the Licensed Product, and not for commercial sale, FRESENIUS shall provide the clinical supplies of Licensed Product to NABI: (i) for the conduct of clinical trial(s) to support the approval of the first [*****] indication in each area of [*****] and for the conduct of clinical trial(s) for the approval of the first [*****]; and (ii) for all other indications (e.g. [*****]) or for extensions of existing approvals (e.g. different dose regimens) at a price of [*****]. Commencing with January 1, 2007, such amount shall be increased, but not decreased, on each January 1 by the rate of increase of inflation as measured by the change in the Inflation Factor between January 1 of the new year and January 1 of the preceding year. Such Licensed Product shall be manufactured in compliance with GMP and the specifications set forth on Schedule A (as such specifications may be changed by the parties in consultation with the US FDA).

5.2. Commercial Supplies

FRESENIUS will supply to NABI its requirements of Licensed Product for commercial sale in a timely manner which are ordered in accordance with this Agreement. Such Licensed Product shall be manufactured in accordance with, and when Delivered shall comply with, specifications which are mandated by the US FDA and each other applicable governmental agency or legislative changes for commercialization in the Territory (the “ Specifications ”). Such Licensed Product shall be manufactured in compliance with, and when Delivered shall comply with, GMP and any other applicable laws and regulations applicable to Licensed Product to be marketed in the Territory. The price for commercial supplies of the Licensed Product is set forth in Section 7.3 below. When License Product is Delivered, the expiration date of the Licensed Product must be no sooner than the expiration date specified in the BLA minus nine (9) months.

5.3. Manufacture

A. Within one hundred twenty (120) days of the execution of this Agreement, the respective quality control representatives of the parties shall meet and negotiate in good faith a Quality Agreement, to be signed by authorized representatives of each party. The Quality Agreement is intended to address those items as are customary for such agreements in the United States pharmaceutical industry including, but not limited to, changes to the Specifications and other change control issues, certifications of compliance and analysis, review of batch records, and other such quality matters. In the event of a conflict between the Quality Agreement and this Agreement, this Agreement shall control.

B. After the US FDA grants marketing approval for the Licensed Product, FRESENIUS shall maintain inventory of finished Licensed Product for sale by NABI in the Territory as agreed by the parties from time to time but at all times at least equal to the number of [*****] vials of Licensed Product Delivered to NABI during the prior [*****].

 

- 13 -

5.4. Forecasts

A. Commencing in March 2007, NABI shall provide FRESENIUS on a monthly basis by the tenth (10 ^th ) day of each month with a rolling twelve (12) month forecast of its estimated requirements of Licensed Product provided that such estimate shall not constitute a binding order or commitment. At all times NABI shall place firm orders at least twenty-six (26) weeks in advance of the requested date of Delivery.

B. Before BLA approval, FRESENIUS shall not be required, in respect of each rolling 12-month period, to fill firm orders of more than [*****] of the quantity previously forecasted by NABI in its rolling twelve (12) month forecast for such period, nor shall it be required to fill any order placed less than twenty-six (26) weeks preceding the requested Delivery date. FRESENIUS shall use commercially reasonable efforts, but shall not be obligated, to fill firm orders for quantities in excess of [*****].

C. After BLA approval, FRESENIUS shall not be required, in respect of each following 12-month period, to fill firm orders of more than [*****] of the quantity previously forecasted by NABI in its rolling twelve (12) month forecast for such period, nor shall it be required to fill any order placed less than twenty-six (26) weeks preceding the Delivery date. FRESENIUS shall use commercially reasonable efforts, but shall not be obligated, to fill firm orders for quantities in excess of [*****]. Between March 1 ^st and April 1 ^st of each year commencing with 2008, NABI shall provide FRESENIUS with a good faith non-binding forecast for an additional twelve (12) month period.

5.5. Information Required on Purchase Orders

Orders shall be placed by NABI with FRESENIUS and shall specify quantities ordered, delivery dates, and delivery and shipping instructions. The obligations and rights of the parties shall be governed by the terms and conditions of this Agreement. Any terms or provisions contained or referred to in NABI’s purchase orders which deal or purport to deal with any rights, obligations or issues other than those specified in this Agreement shall be of no force or effect, unless agreed to in writing by FRESENIUS.

5.6. Product Labeling

NABI and FRESENIUS shall discuss and mutually agree upon any packaging artwork, labeling artwork, packaging specifications and labeling specifications for the Licensed Product. In addition, all Licensed Product shall carry the trade name and markings to indicate that the Licensed Product is manufactured by FRESENIUS, and any additional markings as may be required by applicable law, provided that the parties agree that the marks “ATG North America”, “ATG NA” and “EZ 2053” shall not be utilized without NABI’s written consent. To the extent permitted by applicable law, NABI’s name and brand livery shall be the predominant livery

 

- 14 -

displayed on the label in a manner that is consistent with customary industry practice. FRESENIUS shall procure the required labeling, and shall label and package the Licensed Product prior to shipment in accordance with such artwork, packaging and labeling specifications.

5.7. Batch Documentation; Certificate of Analysis

A. FRESENIUS shall maintain and provide to NABI an English translation of the master batch record maintained by FRESENIUS from time-to-time. At least ten (10) Business Days prior to each Delivery, FRESENIUS shall deliver to NABI a copy of all the batch documentation for the product being Delivered which shall include batch production records and manufacturing and analytical records and copies of all process deviations associated therewith, if any.

B. At the time of each Delivery of Licensed Products FRESENIUS shall provide NABI with an original sig