CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS,
HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.
EXHIBIT 99.1
PROCESS DEVELOPMENT AND MANUFACTURING AGREEMENT
BETWEEN
XOMA (US) LLC
AND
ONYX PHARMACEUTICALS, INC.
JANUARY 29, 2001
TABLE OF CONTENTS
PAGE
1. DEFINITIONS..............................................................................1
1.1 "Acceptance Period".............................................................1
1.2 "Affiliate".....................................................................1
1.3 "Attainment of Commercial Scale"................................................1
1.4 "Batch".........................................................................2
1.5 "BLA"...........................................................................2
1.6 "cGMP"..........................................................................2
1.7 "Commercial Scale"..............................................................2
1.8 "Confidential Information"......................................................2
1.9 "Control", "Controls" and "Controlled"..........................................2
1.10 "Delivery Date".................................................................2
1.11 "Development Phase".............................................................2
1.12 "Development Scale".............................................................2
1.13 "Drug Substance"................................................................2
1.14 "Facility"......................................................................2
1.15 "FDA"...........................................................................2
1.16 "FD&C Act"......................................................................2
1.17 "Fully Burdened Staffing Costs".................................................2
1.18 "IND"...........................................................................3
1.19 "Intellectual Property Rights"..................................................3
1.20 "Innovations"...................................................................3
1.21 "Letter Agreement"..............................................................3
1.22 "Manufacturing Phase"...........................................................3
1.23 "ONYX-015"......................................................................3
1.24 "ONYX-015 Derivative"...........................................................3
1.25 "Onyx Innovations"..............................................................3
1.26 "Onyx Partner"..................................................................3
1.27 "Party" and "Parties"...........................................................3
1.28 "Patents".......................................................................3
1.29 "Project".......................................................................3
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
i.
TABLE OF CONTENTS
(CONTINUED)
1.30 "Project Innovations"...........................................................3
1.31 "Project Team"..................................................................3
1.32 "Regulatory Approval"...........................................................3
1.33 "Regulatory Authority"..........................................................4
1.34 "Shelf Life"....................................................................4
1.35 "Specifications"................................................................4
1.36 "Suite".........................................................................4
1.37 "Third Party"...................................................................4
1.38 "Work Plan".....................................................................4
1.39 "XOMA Innovations"..............................................................4
1.40 "Yield".........................................................................4
2. OVERVIEW AND GOVERNANCE OF MANUFACTURING RELATIONSHIP....................................4
2.1 Project; Committed Resources; Schedule..........................................4
2.2 Work Plan.......................................................................5
2.3 Project Team....................................................................5
2.4 Senior Management Oversight and Dispute Resolution..............................6
2.5 Specifications; Changes to Specifications and Work Plan.........................6
2.6 Onyx Representatives............................................................7
2.7 Non-Exclusive Relationship......................................................7
2.8 Non-Solicitation and Non-Hire Obligations.......................................7
2.9 Compliance with Laws............................................................7
3. FACILITIES AND EQUIPMENT.................................................................7
3.1 Dedicated Manufacturing Suite...................................................7
3.2 Additional Equipment and Facility Modifications.................................8
(a) Development Phase Equipment Purchases..................................8
(b) Manufacturing Phase Equipment Purchases................................8
(c) Suite Modifications....................................................8
3.3 Replacement Suite...............................................................8
3.4 Compliance Audit................................................................9
4. TECHNOLOGY TRANSFER, SCALE-UP, PURIFICATION AND PROCESS DEVELOPMENT......................9
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
ii.
TABLE OF CONTENTS
(CONTINUED)
4.1 Manufacturing Technology Transfer to XOMA.......................................9
4.2 Scale-up of Manufacture.........................................................9
(a) Establishment of Commercial Scale......................................9
(b) Additional Registration Batches........................................9
(c) Non-Attainment of [ * ]L Scale........................................10
4.3 Production at Development Scale................................................10
5. CLINICAL AND COMMERCIAL SUPPLY; REGULATORY MATTERS......................................10
5.1 Raw Materials Services; In-Process Testing.....................................10
5.2 Minimum Batch Manufacture......................................................11
(a) First Year............................................................11
(b) Subsequent Years......................................................11
(c) Additional Batches....................................................11
(d) Reductions in Minimum Batch Commitments...............................11
(e) Increases in Capacity for Drug Substance Manufacture..................11
5.3 Orders and Supply..............................................................12
(a) General...............................................................12
(b) Purchase Orders.......................................................12
(c) Cancellations.........................................................12
(d) Rescheduling..........................................................12
5.4 Commercial Supply Forecast.....................................................12
5.5 Delivery.......................................................................12
5.6 Testing, Acceptance and Rejection..............................................13
5.7 Regulatory Changes.............................................................14
5.8 Change in Manufacturing Process................................................14
5.9 Samples........................................................................14
5.10 Regulatory Matters.............................................................14
6. PRICES AND PAYMENT......................................................................15
6.1 Upfront Payment................................................................15
6.2 Space Fee......................................................................15
6.3 Equipment and Facility Reimbursement...........................................15
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
iii.
TABLE OF CONTENTS
(CONTINUED)
6.4 Personnel Costs................................................................15
(a) Development Phase.....................................................15
(b) Manufacturing Phase...................................................15
(c) Regulatory Work.......................................................15
(d) Post-Termination or -Expiration Technology Transfer...................16
6.5 Milestone Payments.............................................................16
(a) Initial Commercial Scale Batch Meeting Specifications and
with Adequate Yield...................................................16
(b) Yield Improvements....................................................16
(c) Regulatory Approval for Facility......................................16
6.6 Commercial Scale Batch Payments................................................17
(a) Batch Price...........................................................17
(b) Additional Batches....................................................17
(c) Adjustments...........................................................17
(d) Additional Orders at Commercial Scale.................................17
6.7 Payment........................................................................17
6.8 Records........................................................................17
6.9 Taxes Withheld.................................................................18
7. TECHNOLOGY AND INFORMATION..............................................................18
7.1 Technology Transfer............................................................18
(a) Periodic Updates......................................................18
(b) Expiration, Termination or upon Request...............................18
7.2 Information....................................................................19
(a) Documentation.........................................................19
(b) Access................................................................19
(c) Audit of Records......................................................19
7.3 Licenses.......................................................................19
(a) Development and Manufacturing License to XOMA.........................19
(b) Project Innovations License to XOMA...................................19
(c) XOMA Innovations License to Onyx......................................19
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
iv.
TABLE OF CONTENTS
(CONTINUED)
7.4 Ownership of Innovations and Intellectual Property.............................20
(a) Third Party Technology................................................20
(b) Onyx Innovations......................................................20
(c) XOMA Innovations......................................................20
(d) Project Innovations...................................................20
7.5 Patenting of Project Innovations...............................................20
7.6 Infringement of Patents........................................................21
8. REPRESENTATIONS AND WARRANTIES; DISCLAIMERS.............................................22
8.1 Drug Substance Warranties and Remedy...........................................22
(a) Warranties............................................................22
(b) Remedy................................................................22
8.2 General Representations and Warranties.........................................22
(a) Corporate Existence and Power.........................................22
(b) Authority and Binding Agreement.......................................22
(c) Title.................................................................23
8.3 Warranty Disclaimer............................................................23
9. INDEMNIFICATION; LIMITATION OF LIABILITY................................................23
9.1 Onyx Indemnity.................................................................23
9.2 XOMA Indemnity.................................................................23
9.3 Separate Defenses..............................................................23
9.4 Expenses.......................................................................24
9.5 Limitation of Liability........................................................24
10. CONFIDENTIALITY.........................................................................24
10.1 Confidential Information; Exceptions...........................................24
10.2 Authorized Disclosure..........................................................25
10.3 Press Releases.................................................................26
10.4 Requests for Confidential Treatment............................................26
10.5 Return of Confidential Information.............................................26
10.6 Injunctive Relief..............................................................26
10.7 Survival.......................................................................26
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
v.
TABLE OF CONTENTS
(CONTINUED)
10.8 Superseding Effect.............................................................27
11. TERM AND TERMINATION....................................................................27
11.1 Term...........................................................................27
11.2 Termination by XOMA............................................................27
11.3 Termination by Onyx............................................................27
(a) Delay in Performance by XOMA..........................................27
(b) For Convenience Before Attainment of Commercial Scale.................28
(c) For Convenience After Attainment of Commercial Scale..................28
11.4 Breach.........................................................................29
11.5 Technology Transfer............................................................29
11.6 Surviving Obligations..........................................................29
12. MISCELLANEOUS...........................................................................29
12.1 Notice.........................................................................29
12.2 Use of Names...................................................................30
12.3 Formal Dispute Resolution......................................................30
(a) Arbitration...........................................................30
(b) Intellectual Property Disputes........................................31
12.4 Rights in Bankruptcy...........................................................31
12.5 Waiver.........................................................................32
12.6 Assignment; Binding Effect.....................................................32
12.7 Independent Parties............................................................32
12.8 Force Majeure..................................................................32
12.9 Severability...................................................................32
12.10 Governing Law..................................................................33
12.11 Entire Agreement; Modification.................................................33
12.12 Counterparts...................................................................33
EXHIBIT A SPECIFICATIONS................................................................A-1
EXHIBIT B SUITE.........................................................................B-1
EXHIBIT C PRESS RELEASES................................................................C-1
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
vi.
PROCESS DEVELOPMENT AND MANUFACTURING AGREEMENT
THIS AGREEMENT (the "AGREEMENT") is made effective as of the 29th day
of January, 2001 ("EFFECTIVE Date"), by and between XOMA (US) LLC, a Delaware
limited liability company ("XOMA"), with offices at 0000 Xxxxxxx Xxxxxx,
Xxxxxxxx, Xxxxxxxxxx 00000, XXX, and ONYX PHARMACEUTICALS, INC., a Delaware
corporation ("ONYX"), with offices at 0000 Xxxxxxxx Xxxxx, Xxxxxxxx, Xxxxxxxxxx
00000, XXX. XOMA and Onyx are sometimes referred to herein individually as a
"PARTY" and collectively as "PARTIES".
RECITALS
WHEREAS, Onyx, a biotechnology company engaged in the discovery and
development of novel pharmaceuticals for cancer indications, has discovered and,
together with its collaboration partner, Pfizer Inc. ("PFIZER"), is developing a
novel replicating virus, ONYX-015 (also known as CI-1042 and further defined
below), as a biopharmaceutical product now in Phase III clinical trials.
Currently, ONYX-015 is manufactured at small scale by contract manufacturers;
WHEREAS, XOMA is a company that has developed substantial expertise in
process development, scale-up, and small- and large-scale manufacturing of its
own and its partners' biopharmaceutical products, and, in addition, has invested
in biopharmaceutical manufacturing facilities; and
WHEREAS, Onyx would like to engage XOMA to scale up and improve the
process for the manufacture of ONYX-015 and to manufacture and supply ONYX-015
in bulk form for clinical trials and for the commercial launch of the ONYX-015
product, and XOMA would like to provide such services to Onyx.
NOW, THEREFORE, in consideration of the foregoing premises and the
mutual promises and covenants set forth below, Onyx and XOMA mutually agree as
follows:
1. DEFINITIONS.
As used in this Agreement, the following terms will have the following
meanings:
1.1 "ACCEPTANCE PERIOD" shall have the meaning given such term in
Section 5.6(a).
1.2 "AFFILIATE" means any person or entity that, directly or
indirectly, through one or more intermediaries, Owns, is Owned by or is under
common Ownership with, a Party, where "Own", "Owned" or "Ownership" refers to
(a) direct or indirect possession of at least fifty percent (50%) of the
outstanding voting securities of a corporation or a comparable ownership in any
other type of entity; or (b) the actual ability of an entity, person or group to
control and direct the management of the person or entity, whether by contract
or otherwise.
1.3 "ATTAINMENT OF COMMERCIAL SCALE" shall have the meaning given
such term in Section 4.2(b).
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
1.
1.4 "BATCH" means a specific quantity of Drug Substance that is
intended to have a uniform character and quality, within specified limits, and
that is produced according to a single manufacturing order during the same cycle
of manufacture.
1.5 "BLA" means a Biologics License Application filed with the FDA
or other equivalent application(s) for Regulatory Approval in a jurisdiction
other than the United States of America.
1.6 "CGMP" means the then current standards for manufacture of
biologicals, as set forth in the FD&C Act, and such standards of good
manufacturing practice as are required by the FDA or other Regulatory
Authorities with jurisdiction where ONYX-015 will be used in clinical trials or
commercialized.
1.7 "COMMERCIAL SCALE" means the [ * ]L nominal volume
fermentation bioreactor production scale for the ONYX-015 manufacturing process
that will result from scale-up work during the Development Phase, as it may be
modified pursuant to Section 4.2(c).
1.8 "CONFIDENTIAL INFORMATION" shall have the meaning given such
term in Section 10.1.
1.9 "CONTROL", "CONTROLS" and "CONTROLLED" mean, with respect to a
particular item of information or Intellectual Property Right, that the
applicable Party owns or has a license to such item or right and has the ability
to grant to the other Party access to and a license or sublicense (as
applicable) under such item or rights as provided for herein without violating
the terms of any agreement or other arrangement with any Third Party.
1.10 "DELIVERY DATE" shall have the meaning given such term in
Section 5.3(a).
1.11 "DEVELOPMENT PHASE" shall have the meaning given such term in
Section 2.2.
1.12 "DEVELOPMENT SCALE" means the [ * ]L, [ * ]L or comparable
nominal volume fermentation bioreactor production scales for the Drug Substance
manufacturing process transferred to XOMA and further developed under this
Agreement.
1.13 "DRUG SUBSTANCE" means a formulation of purified bulk ONYX-015
that has been manufactured and processed to the stage where it is suitable for
fill-and-finish procedures yielding the ONYX-015 product suitable for release
for use in clinical trials or commercial sales.
1.14 "FACILITY" shall have the meaning given such term in Section
3.1.
1.15 "FDA" means the United States Food and Drug Administration, or
any successor agency.
1.16 "FD&C ACT" means the United States Food, Drug and Cosmetics
Act and applicable regulations and guidances promulgated thereunder, as amended
from time to time.
1.17 "FULLY BURDENED STAFFING COSTS" shall have the meaning given
such term in Section 6.4(a).
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
2.
1.18 "IND" means an Investigational New Drug application as defined
in the FD&C Act and/or its equivalent in any country other than the United
States of America, the filing of which is necessary to commence clinical testing
of pharmaceutical products in humans.
1.19 "INTELLECTUAL PROPERTY RIGHTS" means patents, copyrights,
trademarks, service marks, trade secrets, mask works, and applications for the
foregoing, in any country, supranational organization or territory of the world.
1.20 "INNOVATIONS" means inventions, discoveries, works of
authorship, trade secrets and other know-how or developments.
1.21 "LETTER AGREEMENT" shall have the meaning given such term in
Section 2.1(a).
1.22 "MANUFACTURING PHASE" shall have the meaning given such term
in Section 2.2.
1.23 "ONYX-015" means the formulation of the genetically engineered
adenovirus DL1520 described in US Patent Numbers 5,677,178 and 5,846,945,
selected by ONYX, that is currently in Phase III clinical trials.
1.24 "ONYX-015 DERIVATIVE" means ONYX-015 derivatized by
engineering the ONYX-015 genome to contain one or more additional transgenes
that code for one or more protein(s).
1.25 "ONYX INNOVATIONS" shall have the meaning given such term in
Section 7.4(b).
1.26 "ONYX PARTNER" means any Third Party collaboration partner of
Onyx pursuant to a written agreement for the development and/or
commercialization of the ONYX-015 product, of which partner Onyx has given
written notice to XOMA. For clarity, Onyx's Third Party collaboration partner
for such purposes as of the Effective Date is Pfizer.
1.27 "PARTY" and "PARTIES" shall have the meanings given such
terms, respectively, in the first paragraph of this Agreement.
1.28 "PATENTS" means (i) United States issued patents,
re-examinations, reissues, renewals, extensions, patent term restorations, and
foreign counterparts of each of the foregoing; and (ii) pending applications for
United States patents and foreign counterparts thereof, whether issued or not.
1.29 "PROJECT" shall have the meaning given such term in Section
2.1.
1.30 "PROJECT INNOVATIONS" shall have the meaning given such term
in Section 7.4(d)(i).
1.31 "PROJECT TEAM" shall have the meaning given such term in
Section 2.3.
1.32 "REGULATORY APPROVAL" means all approvals, product and/or
establishment licenses, registrations or authorizations of all supranational,
national or local regulatory agencies
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
3.
and other governmental entities, necessary for the manufacture, use, storage,
import, export, transport and sale of a biological product in a jurisdiction.
1.33 "REGULATORY AUTHORITY" means a supranational, national or
local regulatory agency or other governmental entity with the authority to grant
a Regulatory Approval.
1.34 "SHELF LIFE" means the length of time that Drug Substance can
be stored at conditions measured and documented as set forth in the
Specifications, as set forth in any BLA for ONYX-015, as it may be amended or
any Regulatory Approval for ONYX-015.
1.35 "SPECIFICATIONS" means the specifications and testing
procedures for Batches of Drug Substance manufactured under this Agreement, as
set forth in Exhibit A and as amended from time to time pursuant to Section 2.5.
1.36 "SUITE" shall have the meaning given such term in Section 3.1.
1.37 "THIRD PARTY" means any person or entity other than the
Parties or their respective Affiliates.
1.38 "WORK PLAN" shall have the meaning given such term in Section
2.2.
1.39 "XOMA INNOVATIONS" shall have the meaning given such term in
Section 7.4(c).
1.40 "YIELD" means the percentage ratio of the number of particles
of ONYX-015 in the purified Drug Substance to the number of particles of
ONYX-015 in the initial crude virus homogenate of the cells harvested from the
fermentation bioreactor batch.
2. OVERVIEW AND GOVERNANCE OF MANUFACTURING RELATIONSHIP.
2.1 PROJECT; COMMITTED RESOURCES; SCHEDULE. XOMA and Onyx are
entering into a strategic manufacturing relationship (the "PROJECT"), with the
purpose of XOMA producing clinical and commercial supplies of Drug Substance in
compliance with Specifications at Commercial Scale for Onyx. Subject to the
terms and conditions of this Agreement, XOMA will carry out the Project in
accordance with this Agreement and the Work Plan (as defined in Section 2.2) and
in full compliance with cGMP. XOMA will commit to the Project appropriate
personnel (including without limitation those with expertise in technical
development, manufacturing, operations, quality control, quality assurance and
regulatory affairs) and appropriate facilities in its biopharmaceutical
manufacturing facility located in Berkeley, California. Onyx will commit such of
its personnel with appropriate expertise to provide monitoring and, as
appropriate, technical consultation for the Project. XOMA and Onyx recognize the
importance of timely execution of the Project and accordingly each will give
priority to the Project, assign adequate staffing and other resources and use
all diligent, commercially reasonable efforts to maximize the potential of
achieving successful completion of the Project (including without limitation
timely provision of all deliverables in accordance with the Work Plan) according
to the following schedule:
(a) The Parties have initiated certain aspects of the
Project prior to the Effective Date pursuant to the Letter Agreement by and
between them dated January 12, 2001
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
4.
(the "LETTER AGREEMENT"). Onyx and XOMA each will give priority to
completion, as promptly as reasonably practicable, of (i) the transfer of
technology relating to the manufacture of Drug Substance from Onyx and its
Third Party manufacturers to XOMA, (ii) the planning and implementation of
the Development Phase, and (iii) the initial planning for the Manufacturing
Phase.
(b) Beginning in [ * ], XOMA plans to initiate
Development Scale production of Drug Substance in the Suite, which shall be
dedicated to the production of Drug Substance under this Agreement. As
reasonably requested by XOMA, Onyx will provide raw materials, buffers, media,
cell banks and viral banks that have been released by Onyx quality assurance
and/or quality control personnel and will provide certificates of analysis
therefor.
(c) Upon completion of manufacture of Batches of Drug
Substance at Development Scale, in approximately [ * ] depending on how many
Batches are agreed to by the Parties, XOMA plans to initiate development work
for process improvements that further scale up the ONYX-015 manufacturing
process and increase the Yield of ONYX-015. Onyx will make available reasonable
numbers of its scientific staff from its Process Sciences group with appropriate
expertise to participate in this work, if needed by XOMA.
(d) Upon completion of Development Phase work, XOMA plans
to implement the process improvements and expects to produce the first
Commercial Scale Batch pursuant to Section 4.2(a) in approximately [ * ].
(e) Throughout the Development Phase, Onyx will make
scientific and technical staff available as necessary and reasonably useful to
assist XOMA's efforts.
(f) The Parties anticipate that XOMA will commence the
manufacture of the second and third registration Batches pursuant to Section
4.2(b) in approximately [ * ].
2.2 WORK PLAN. As soon as practicable, but in any case within 45
days after the Effective Date, Onyx and XOMA shall develop a mutually agreed,
detailed work plan (the "WORK PLAN") for the technology transfer, scale-up,
purification, and process development work to be carried out pursuant to Section
4 through production of the first registration Batch at Commercial Scale
pursuant to Section 4.2(a) (the "DEVELOPMENT PHASE"), and for the Commercial
Scale manufacturing to be carried out pursuant to Section 5 beginning with the
second registration Batch pursuant to Section 4.2(b) (the "MANUFACTURING
PHASE"). The Project Team members shall review the Work Plan and consult as to
its continuing suitability at their meetings pursuant to Section 2.3 and shall
implement any revisions thereto that are mutually acceptable to both Parties.
2.3 PROJECT TEAM. Promptly after the Effective Date, the Parties
will form a Project Team ("PROJECT TEAM"), with each Party designating two (2)
members of the Project Team. Each Party may replace or supplement its members on
the Project Team and will at all times ensure that its current Project Team
members have expertise appropriate to the current stage of the Project. The
Project Team will be responsible for reviewing progress of the Project under the
Work Plan and to discuss and decide on any potential revisions to the Work Plan.
The Project Team may make decisions only by the unanimous consensus of all
members thereof. If there are
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
5.
any matters on which the Project Team is unable to achieve consensus, either
Party's Project Team members may refer the matter to the CEOs of both Parties
as further described in Section 2.4. During the Development Phase, the
Project Team shall hold meetings as agreed by Project Team members or as
requested by either Party. During the Manufacturing Phase, the Project Team
shall hold meetings as agreed by Project Team members or as requested by
either Party to review the progress of ONYX-015 in clinical development and
the status of manufacturing of ONYX-015 for clinical and commercial supply.
2.4 SENIOR MANAGEMENT OVERSIGHT AND DISPUTE RESOLUTION. Members of
the senior management of Onyx and XOMA will hold meetings as agreed by such
persons or as requested by either Party at least annually to review the status
of the Project and progress under the Work Plan. In addition, if members of the
Project Team refer any matters to the CEOs of the Parties pursuant to Section
2.3, then (i) for matters involving the definition or contents of the Work Plan
or the Specifications or re-designation of the Commercial Scale pursuant to
Section 4.2(c), the CEOs of the Parties will consult in good faith as to such
matter, and the Onyx CEO will determine the resolution thereof in his or her
sole discretion, subject to the provisions of Section 2.5(b), or (ii) for any
other matter, the CEOs of the Parties will attempt in good faith to resolve such
matter for thirty (30) days.
2.5 SPECIFICATIONS; CHANGES TO SPECIFICATIONS AND WORK PLAN.
(a) As of the Effective Date, Onyx and Pfizer have agreed
upon the current Specifications for Drug Substance, which are attached hereto as
Exhibit A. Onyx may change the Specifications from time to time, after
consulting with XOMA in advance as to such changes, and such revised
Specifications shall replace the previous Specifications and shall be deemed to
be part of this Agreement as Exhibit A. In particular, the Parties expect that
Onyx will change the Specifications as a result of process changes made during
the Development Phase under Section 4 and the data obtained from registration
Batches manufactured pursuant to Section 4.2, and that such modified
Specifications will be consistent with FDA expectations for purity, potency, and
other product characteristics. Onyx and XOMA expect that the modified
Specifications will be comparable to Specifications existing as of the Effective
Date, particularly as regards purity and potency.
(b) Onyx shall be responsible for any incremental costs
incurred by XOMA as a result of any changes to the Specifications or the Work
Plan pursuant to clause (i) of Section 2.4 or to Section 2.5(a). If such changes
significantly and adversely affect the ability of XOMA to manufacture Drug
Substance in compliance with Specifications or require significant modifications
to the Suite in order to permit XOMA to manufacture Drug Substance in accordance
with the Specifications, then at XOMA's election, the Parties will undertake,
diligently and in good faith, such of the following as is appropriate in light
of the changes in the Specifications: (i) the Parties will renegotiate the terms
of this Agreement so as to permit XOMA to perform its obligations under this
Agreement with substantially the same economic benefit for its efforts; (ii) the
Parties will agree upon an extension of the timeframes in Section 11.3(a)
pursuant to which Onyx may terminate the Agreement without penalty; and/or (iii)
the Parties will agree upon an extension of the period during which XOMA will
manufacture the guaranteed minimum number of Batches so as to permit XOMA to
recapture its economic benefits as contemplated in this Agreement.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
6.
2.6 ONYX REPRESENTATIVES. Onyx shall be allowed to have, at its
cost, up to two (2) representatives, escorted by XOMA personnel, with full
access to the Suite during the manufacture of ONYX-015 for the purpose of
observing, reporting on, and consulting as to such manufacturing efforts. Prior
to receiving such access, such representatives will enter into XOMA's standard
form of confidentiality agreement, which will be commercially reasonable and
will permit such representatives to disclose information learned to Onyx,
Pfizer, and any other Onyx Partner approved in writing in advance by XOMA, such
approval not to be unreasonably withheld. XOMA will reasonably cooperate in
enabling such representatives to carry out their responsibilities and will make
adequate temporary desk space and other reasonable resources available to these
representatives during the periods they are working at XOMA.
2.7 NON-EXCLUSIVE RELATIONSHIP. The manufacturing relationship set
forth in this Agreement will be non-exclusive. Onyx is presently obtaining
ONYX-015 from two contract manufacturers and, subject to its compliance with the
minimum purchase requirements of this Agreement, Onyx shall have the right to
establish additional manufacturing arrangements with these parties or new
arrangements with other parties.
2.8 NON-SOLICITATION AND NON-HIRE OBLIGATIONS. During the term of
this Agreement and for two (2) years after expiration or termination hereof,
without the other Party's prior written consent, neither Onyx nor XOMA shall
solicit for employment or for an independent contractor relationship, hire as an
employee, or enter into an independent contractor relationship with, any persons
who are currently employed by the other Party or who, at any time during the
term of this Agreement, are employed by the other Party; PROVIDED, HOWEVER, that
nothing in this Section 2.8 shall restrict a Party from soliciting, employing or
engaging as an independent contractor any former employee of the other Party who
is at such time employed by a Third Party.
2.9 COMPLIANCE WITH LAWS. In carrying out its obligations under
this Agreement, each Party will comply with all material laws, regulations,
requirements and orders of any and all United States federal, state and local
authorities and agencies (including without limitation all laws and regulations
of such territories applicable to the transportation, storage, use, handling and
disposal of hazardous materials) applicable to the manufacture of ONYX-015 and
the Facility. XOMA will maintain during the term of this Agreement all
government permits, including without limitation health, safety and
environmental permits, necessary for the conduct of the actions and procedures
that it undertakes pursuant to this Agreement.
3. FACILITIES AND EQUIPMENT.
3.1 DEDICATED MANUFACTURING SUITE. XOMA will dedicate, exclusively
to the Project, the manufacturing suite identified in Exhibit B (the "SUITE"),
and equipment at its biopharmaceutical manufacturing facility at 0000 Xxxxxxx
Xxxxxx, Xxxxxxxx, Xxxxxxxxxx (the "FACILITY"). The equipment shall include
bioreactors with [ * ]L, [ * ]L, and [ * ] nominal volumes and [ * ]L, [ * ]L
and [ * ]L approximate working volumes, respectively, dedicated cell culture,
fermentation and purification space, and all other equipment specified in the
Work Plan. The Suite will remain dedicated exclusively to the Project during the
term of this Agreement, including any extensions thereto.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
7.
3.2 ADDITIONAL EQUIPMENT AND FACILITY MODIFICATIONS.
(a) DEVELOPMENT PHASE EQUIPMENT PURCHASES. The Parties
acknowledge that certain equipment must be obtained for the Development Phase,
some of which will be specified in the initial Work Plan and some of which will
not be identifiable when the initial Work Plan is adopted. During the
Development Phase, XOMA shall purchase for its own account and for delivery to
the Facility, all equipment that is to be dedicated to the Project during the
Development Phase, as either set forth in the Work Plan or approved in writing
in advance by Onyx, which approval shall not be unreasonably withheld. Onyx will
reimburse XOMA for such equipment purchases pursuant to Section 6.3. If such
equipment is not used for the Project or for other Onyx products, then upon the
Parties' mutual agreement, either XOMA will transfer the equipment to Onyx at [
* ], or XOMA will reimburse Onyx for the equipment at its [ * ], but if the
Parties do not reach agreement within thirty (30) days, XOMA will transfer the
equipment to Onyx at [ * ]. Onyx will pay any costs of the physical transfer of
such equipment to Onyx.
(b) MANUFACTURING PHASE EQUIPMENT PURCHASES. Before
production of the first batch of ONYX-015 at Commercial Scale in accordance with
Section 4.2(a), it may be necessary to obtain additional equipment dedicated to
the Project for manufacture of clinical and commercial supplies of ONYX-015 at
Commercial Scale (e.g. replacement columns). XOMA will purchase for its own
account and for delivery to the Facility any such additional dedicated equipment
for the Project during the Manufacturing Phase, as either set forth in the Work
Plan or as approved in advance in writing by Onyx, which approval shall not be
unreasonably withheld. Onyx will reimburse XOMA for such equipment purchases
pursuant to Section 6.3.
(c) SUITE MODIFICATIONS. As set forth in the Work Plan or
upon prior approval of Onyx, XOMA will make modifications to the Suite required
for the Project, and Onyx will reimburse XOMA for the costs thereof pursuant to
Section 6.3. XOMA shall exclusively own all such modifications to the Suite.
3.3 REPLACEMENT SUITE. On a one-time basis, XOMA may elect to give
written notice to Onyx that XOMA wishes to use the Suite for another product of
XOMA or a Third Party, and in the notice XOMA will in good faith represent that
a bona fide conflict exists for XOMA's manufacturing capacity. Within thirty
(30) days of receipt of such notice, Onyx may elect, at its sole option, to
provide XOMA with a one-time fee [ * ], which is intended to defray some of the
costs associated with the construction of a suite reasonably comparable to the
Suite and suitable for cGMP manufacturing within the Facility for the purpose of
accommodating a XOMA or Third Party product. If Onyx provides such a fee to
XOMA, then either (i) XOMA will, within [ * ] of receipt of such fee, select the
site for such suite and prepare drawings for such suite that are approved by
responsible management and are suitable for preparation of schematics for such
suite, and will otherwise complete such additional suite as quickly as
reasonably practicable, or (ii) XOMA will promptly refund the [ * ] fee to Onyx.
If Onyx does not elect to provide XOMA with the one-time [ * ] fee within the
above-referenced thirty (30) day period, XOMA may terminate this Agreement upon
at least [ * ] months prior written notice pursuant to Section 11.2(b).
3.4 COMPLIANCE AUDIT. XOMA acknowledges that, promptly following
the Effective Date, Pfizer representatives will perform a regulatory compliance
audit of the Suite and the
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
8.
Facility for purposes of this Agreement, and XOMA will provide access during
reasonable business hours to Pfizer and Onyx representatives for such purpose
and will otherwise reasonably cooperate with such audit. If Pfizer identifies
any deficiencies in either the Facility or XOMA manufacturing processes, XOMA
will take any corrective measures reasonably requested by Pfizer and approved
by Onyx, at Onyx's cost. XOMA will similarly cooperate with a reasonable
number of future regulatory compliance audits by Onyx or Onyx Partners at a
reasonable frequency; PROVIDED, HOWEVER, that if XOMA does not approve of
such Onyx Partner in writing in advance (such approval not to be unreasonably
withheld), a mutually agreed Third Party shall conduct such audit. Prior to
any audit under this Section 3.4, the applicable representatives will enter
into XOMA's standard form of confidentiality agreement, which will be
commercially reasonable and will permit such representatives to disclose the
audit results to Onyx and the applicable Onyx Partner.
4. TECHNOLOGY TRANSFER, SCALE-UP, PURIFICATION AND PROCESS DEVELOPMENT.
4.1 MANUFACTURING TECHNOLOGY TRANSFER TO XOMA. The Parties have
initiated under the Letter Agreement, and will continue and complete as quickly
as practicable, the transfer of all relevant technology for the manufacture of
ONYX-015 at Development Scale from Onyx and its Third Party manufacturers to
XOMA.
4.2 SCALE-UP OF MANUFACTURE.
(a) ESTABLISHMENT OF COMMERCIAL SCALE. In accordance
with the Work Plan and as quickly as reasonably practicable, XOMA will scale
up the manufacturing scale for Drug Substance to Commercial Scale, including,
without limitation, performing process development work to improve the
manufacturing process for Drug Substance that is transferred to XOMA pursuant
to Section 4.1, increasing of the Drug Substance Yield, and addressing FDA
expectations for quality (i.e., purity and potency). The goal of such efforts
will be the production of the first Batch at Commercial Scale of Drug
Substance that meets Specifications and that results in an overall Drug
Substance Yield of at least [ * ] (which Yield level will not be deemed
pursuant to this Section 4.2(a) to be a Specification). This minimum Yield
percentage of [ * ] is an estimate based on production at the [ * ]L
fermentation bioreactor scale, and it is subject to confirmation and mutually
agreed good faith adjustment by the Parties based upon initial manufacturing
runs at Development Scale.
(b) ADDITIONAL REGISTRATION BATCHES. In accordance with
the Work Plan and as quickly as reasonably practicable after production of the
initial Batch at Commercial Scale pursuant to Section 4.2(a), XOMA will (i)
manufacture a minimum of an additional [ * ] Batches at Commercial Scale with a
Yield of at least [ * ] (as such Yield level may be adjusted pursuant to Section
4.2(a), and which Yield level will not be deemed pursuant to this Section 4.2(b)
to be a Specification) that meet then-current Specifications in compliance with
cGMP, as required to support the preparation and filing of appropriate
documentation with FDA and other Regulatory Authorities to permit the use of
these Batches and additional Batches manufactured at Commercial Scale for human
clinical trials, and (ii) lock-down such scaled-up manufacturing process for
Drug Substance for purposes of filing a BLA for ONYX-015 product. Successful
manufacture of such [ * ] Batches at Commercial Scale and the related lock-down
set forth in Sections 4.2(a) and 4.2(b)(i) and (ii) collectively shall
constitute "ATTAINMENT OF COMMERCIAL
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
9.
SCALE". Onyx, in consultation with XOMA, will use data from at least [ * ]
Commercial Scale Batches to finalize the Specifications consistent with FDA
expectations for purity, potency and other ONYX-015 product characteristics.
(c) NON-ATTAINMENT OF [ * ]L SCALE. If either Party
believes that it will not be commercially feasible to attain and implement the
[ * ]L nominal volume fermentation bioreactor production scale for the ONYX-015
manufacturing process, the Parties will consult in good faith as to the
feasibility of attaining such manufacturing scale. If Onyx, acting in good
faith, determines that it is not commercially feasible to attain such [ * ]L
scale, it may select the [ * ]L Development Scale as the Commercial Scale for
the ONYX-015 manufacturing process for purposes of the filing of the BLA for
ONYX-015, and the Parties will agree in good faith on an equitable adjustment of
the price to be paid by Onyx for each Batch at such revised Commercial Scale.
Furthermore, XOMA will have no obligation to produce more than [ * ] Batches per
calendar year at such [ * ]L Commercial Scale, but the Parties will negotiate in
good faith if Onyx desires Batches in excess of the [ * ] Batches per calendar
year to be provided pursuant to this Section 4.2(c).
4.3 PRODUCTION AT DEVELOPMENT SCALE. Concurrent with scale-up work
pursuant to Section 4.2 and as quickly as reasonably practicable, XOMA will
manufacture according to cGMP [ * ] Batches of Drug Substance at Development
Scale that meet Specifications, in accordance with the Work Plan. XOMA will
retain a portion of such Batches agreed to by the Parties for scale-up work
pursuant to Section 4.2, and Onyx will receive at least half of each such Batch
for purposes of (i) satisfying Onyx and Pfizer's projected needs for a working
supply bank of active ONYX-015 virus and for ONYX-015 supplies for critical
clinical trials, (ii) supporting the preparation and filing of appropriate
documentation (e.g. a Drug Master File or any new or amended INDs for ONYX-015
that Onyx or an Onyx Partner may file), and/or (iii) supporting any BLA that
Onyx or Pfizer may file for ONYX-015. The Parties will consult as to Onyx's
additional needs for Development Scale Batches, based on its needs for the
purposes set forth in this Section 4.3, and XOMA will consider in good faith any
requests by Onyx for such additional production of Drug Substance at Development
Scale, with any production to be included in the Work Plan only upon the
Parties' mutual agreement. If XOMA produces any additional Development Scale
Batch pursuant to this Section 4.3, then: (i) the Parties will agree upon an
extension of the timeframes in Section 11.3(a) pursuant to which Onyx may
terminate this Agreement without penalty; and/or (ii) the Parties will agree
upon an extension of the period during which XOMA will manufacture the
guaranteed minimum number of Batches so as to permit XOMA to recapture its
economic benefits as contemplated in this Agreement.
5. CLINICAL AND COMMERCIAL SUPPLY; REGULATORY MATTERS.
5.1 RAW MATERIALS SERVICES; IN-PROCESS TESTING. After production
of the first Commercial Scale Batch of Drug Substance in accordance with Section
4.2(a), XOMA will provide in accordance with the Work Plan and cGMP, all
ordering, testing, inventorying and releasing services for all raw materials
used in the manufacture of Drug Substance under this Agreement and full
in-process testing for continued manufacture of Drug Substance under this
Agreement. Except for banks of ONYX-015 and host cells reasonably required by
XOMA, XOMA shall obtain all raw materials (e.g. resins, buffers, media, etc.)
for manufacture of Drug
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
10.
Substance under this Section 5, and Onyx shall not be responsible for the
purchase of any such raw materials.
5.2 MINIMUM BATCH MANUFACTURE. Following Attainment of Commercial
Scale, XOMA will manufacture additional Batches of Drug Substance that comply
with the warranties in Section 8.1(a) as follows, subject to Section 4.2(c).
(a) FIRST YEAR. Subject to Sections 5.2(c) and (d),
during the first twelve (12) months following Attainment of Commercial Scale, in
addition to the [ * ] registration Batches described in Section 4.2, XOMA will
manufacture and supply to Onyx, and Onyx will order and purchase, a guaranteed
minimum of [ * ] Batches at Commercial Scale.
(b) SUBSEQUENT YEARS. Subject to Sections 5.2(c) and (d),
XOMA will manufacture and supply to Onyx, and Onyx will order and purchase, a
guaranteed minimum of [ * ] Batches at Commercial Scale during each twelve (12)
month period during the term of this Agreement (including without limitation any
term extensions pursuant to Section 11.1), commencing on an anniversary of the
Attainment of Commercial Scale, or, for any period of less than twelve (12)
months at the end of such term, a number of Batches equal to [ * ] multiplied by
a fraction equal to the number of months in such remaining period divided by 12,
with any fraction to be rounded up or down to the nearest whole number and
fractions of 0.5 to be rounded up to the next whole number.
(c) ADDITIONAL BATCHES. XOMA will fulfill purchase orders
submitted by Onyx in accordance with Section 5.3 for Batches in excess of Onyx's
minimum commitments pursuant to this Section 5.2, up to a maximum of the normal
and commercially reasonable capacity of the Suite (which the Parties agree is at
least [ * ] Batches per year).
(d) REDUCTIONS IN MINIMUM BATCH COMMITMENTS. Onyx shall
have the right during the term of the Agreement, as it may be extended pursuant
to Section 11.1, upon at least six (6) months written notice and upon payment of
a fee of [ * ] of the per-Batch charge as calculated pursuant to Section 6.6, to
reduce the minimum Batch commitment under Section 5.2(a) by up to [ * ] Batches,
and to reduce the minimum Batch commitment under Sections 5.2(b) by up to [ * ]
Batches per year; provided, however, that Onyx may not cancel any firm order
except pursuant to Section 5.3(c).
(e) INCREASES IN CAPACITY FOR DRUG SUBSTANCE MANUFACTURE.
If Onyx determines that the Suite has insufficient capacity for the manufacture
of Drug Substance at Commercial Scale, in light of Onyx and any Onyx Partner's
needs for ONYX-015 product, and Onyx desires that XOMA supply such additional
needs, it will so notify XOMA, and the Parties will negotiate in good faith to
attempt to reach an agreement, the purpose of which would be for XOMA to
manufacture Drug Substance to fulfill Onyx's needs for additional Drug
Substance.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
11.
5.3 ORDERS AND SUPPLY.
(a) GENERAL. During the term of this Agreement, for
each Batch of Drug Substance that XOMA is to supply to Onyx, Onyx will
provide XOMA with a firm, non-cancelable (except as permitted in Section
5.3(c)) purchase order for each Batch at least nine (9) months before the
exact date it wishes such Batch to be delivered by XOMA (the "DELIVERY
DATE"), which Delivery Date shall be specified in the purchase order.
(b) PURCHASE ORDERS. Any purchase order for Drug
Substance that Onyx submits shall reference this Agreement and shall be governed
exclusively by the terms contained in this Agreement. Any term or condition in
any order, confirmation or other document furnished by Onyx or XOMA which is in
any way inconsistent with the terms and conditions of this Agreement is hereby
expressly rejected.
(c) CANCELLATIONS. Subject to Onyx's minimum order and
purchase obligations under Section 5.2, Onyx may cancel any purchase order for
Drug Substance before XOMA begins manufacture of such Batch by providing XOMA
written notice. For any purchase order in excess of Onyx's minimum obligations
under Section 5.2, if Onyx cancels any order for Drug Substance, Onyx shall pay
to XOMA as a cancellation fee [ * ] (i) of the costs of the raw materials
acquired or used in contemplation of fulfilling such order, and (ii) of other
costs reasonably incurred by XOMA that would have been included in the standard
manufacturing cost therefor had such manufacture been completed, in each case
that are incurred up to the time of receipt of such notice. Onyx may change, by
up to two (2) weeks, the Delivery Date for a Batch for which manufacture has
commenced.
(d) RESCHEDULING. Subject to Onyx's minimum order and
purchase obligations under Section 5.2, for any Batch for which XOMA has not
commenced manufacture, Onyx may reschedule a Delivery Date by written notice to
XOMA. For any Batch for which XOMA has commenced manufacture, Onyx may
reschedule a Delivery Date by up to two (2) weeks by written notice to XOMA.
5.4 COMMERCIAL SUPPLY FORECAST. On or before [ * ], Onyx will
provide XOMA with a non-binding written [ * ] year forecast by calendar quarter
of Onyx's or any Onyx Partner's anticipated orders for Drug Substance, based
upon demand for clinical trials and commercial sales and upon reasonably
anticipated dates for issuance of Regulatory Approvals for the ONYX-015 product
and launch dates therefor. This forecast shall be for facility planning purposes
only and shall not constitute an order. Onyx will update this forecast on a
calendar quarterly basis.
5.5 DELIVERY. Unless otherwise agreed by the parties in writing,
on or prior to the applicable Delivery Date XOMA will deliver each Batch of Drug
Substance FCA free carrier the Facility (Incoterms 2000), along with quality
control samples and copies of Batch production records. XOMA will ship each such
Batch to a destination for further fill-and-finish manufacturing and will
provide such samples and copies of Batch production records to Onyx or its
designee, in each case as specified by Onyx in the applicable purchase order.
XOMA will test each Batch of Drug Substance pursuant to Specifications and will
include with each Batch shipped a certificate of analysis confirming that such
Batch meets Specifications. XOMA will
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
12.
package and ship each Batch in accordance with XOMA's customary practices for
pharmaceutical compounds, unless otherwise specified in the applicable
purchase order.
5.6 TESTING, ACCEPTANCE AND REJECTION.
(a) Onyx or its designee may test each Batch of Drug
Substance within thirty (30) days of receipt (the "ACCEPTANCE PERIOD") for
compliance with XOMA's warranties in Section 8.1(a). By the end of the
Acceptance Period, Onyx will either accept such Batch or reject it for
non-compliance with XOMA's warranties in Section 8.1(a). Any such notice of
rejection shall be in writing and shall indicate the reasons for such rejection.
If XOMA does not receive a notice of rejection by the end of the Acceptance
Period, Onyx shall be deemed to have accepted such Batch. Once Onyx accepts a
Batch, Onyx shall have no recourse against XOMA if the product is subsequently
deemed unsuitable for use for any reason, except as provided in Sections 5.6(b)
and (c) and 9.2.
(b) If, after accepting a Batch, Onyx subsequently
discovers or learns of a nonconformity with Specifications that could not
reasonably be detected through the inspection pursuant to Section 5.6(a) or a
latent nonconformity arising after inspection other than those caused by
improper shipping, handling or storage after delivery by XOMA, Onyx may revoke
its acceptance of such Batch by giving written notice to XOMA of the
nonconformity within ten (10) days of discovering it.
(c) After Onyx gives a notice of rejection under Section
5.6(a) or revocation of acceptance under Section 5.6(b), the Parties will
cooperate to determine whether rejection or revocation of acceptance was
necessary or justified. XOMA will evaluate process issues and other reasons for
such potential non-compliance. XOMA will notify Onyx as promptly as reasonably
possible whether it accepts Onyx's basis for any rejection or revocation of
acceptance. If the Parties disagree whether the Batch did not comply with the
warranties in Section 8.1(a), the Parties will submit a sample of such Batch and
applicable documentation to a mutually acceptable independent Third Party
laboratory, which shall make a final and binding determination as to whether
such Batch conforms with the warranties in Section 8.1(a) and thereby as to
whether Onyx's rejection or revocation of acceptance of such Batch was
justified. The Party against whom the Third Party laboratory rules shall bear
all costs of the Third Party testing.
(d) If at the time of Onyx's rejection or revocation of
acceptance of a Batch pursuant to this Section 5.6 the Parties do not agree
whether such rejection or revocation of acceptance was justified under this
Section 5.6, XOMA will use commercially reasonable efforts at Onyx's request to
replace such Batch under appropriate lead times, or, if approved by Onyx, to
rework such Batch so as to comply with the warranties in Section 8.1(a). If the
Third Party laboratory rules pursuant to Section 5.6(c) that a rejected Batch
complied with the warranties in Section 8.1(a), Onyx will purchase the Batch and
any replacement Batch at the price set in this Agreement.
(e) Onyx shall maintain any Batch that it has rejected or
for which it has revoked acceptance until a final determination as to whether
there is a non-conformity with the warranties in Sections 8.1(a), as agreed by
the Parties or as shown by a written notice to that
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
13.
effect from a Third Party laboratory pursuant to Section 5.6(c). At XOMA's
written request, Onyx shall either destroy any finally-rejected Batch
promptly at XOMA's cost and provide XOMA with certification of such
destruction, or promptly return said Batch to XOMA, at XOMA's cost.
5.7 REGULATORY CHANGES. The Parties will promptly notify each
other of any material revisions or amendments of or additions to cGMP and will
confer with each other with respect to the best means to comply with such
requirements. The Parties will allocate any costs of implementing any such
agreed changes on an equitable basis, with Onyx being responsible for costs of
implementation of changes required as a direct result of ONYX-015 being
manufactured at the Facility and XOMA being responsible for costs of
implementation of changes required generally for cGMP manufacture at the
Facility irrespective of the manufacture of ONYX-015, with appropriate
adjustments for any benefits received by the Party not responsible for such
costs.
5.8 CHANGE IN MANUFACTURING PROCESS. XOMA shall obtain Onyx's
prior written approval before it implements any change in the materials,
equipment, process or procedures used to manufacture Drug Substance that would
constitute a major change under cGMP.
5.9 SAMPLES. XOMA shall retain samples of Drug Substance for each
Batch for a period of one (1) year after the expiration date for such Batch. The
sample size shall be twice the size necessary to conduct quality control
testing. Upon Onyx's written request, XOMA shall provide Onyx with up to
one-half the original amount of the retained samples.
5.10 REGULATORY MATTERS. Upon Onyx's or an Onyx Partner's decision
to file a BLA for ONYX-015 with the FDA or Regulatory Authorities in other
countries, and upon Onyx's request, XOMA will, in accordance with the applicable
regulatory requirements, conduct the following activities with respect to the
manufacture by XOMA of Drug Substance at the Suite: (i) conduct process
validation work in support of such BLA(s), (ii) prepare the appropriate portions
of such BLA(s) relating to manufacture of Drug Substance (e.g. the CMC section)
and other appropriate documentation (e.g., an FDA Drug Master File), (iii)
provide Onyx with necessary or reasonably useful rights of reference to such
filings, (iv) in coordination with Onyx, take appropriate responsibility for the
filing and ongoing support of such portions of the BLA(s), including without
limitation regulatory compliance audits and facilities inspections by Onyx
(e.g., mock audits and inspections) and by the FDA and other Regulatory
Authorities, and (v) provide all other reasonable assistance to Onyx in
obtaining Regulatory Approvals for ONYX-015 Products. XOMA will be compensated
for such efforts pursuant to Section 6.4(c). In addition, upon Onyx's request,
XOMA will consider in good faith providing Onyx with additional assistance for
regulatory filings for ONYX-015 with respect to the manufacture of ONYX-015 at
other facilities, subject to its available resources and commitments, provided
that in no event will XOMA be obligated to provide such assistance. Onyx shall
be responsible for all other filings necessary for issuance of Regulatory
Approvals for ONYX-015 products.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
14.
6. PRICES AND PAYMENT.
6.1 UPFRONT PAYMENT. Onyx shall pay XOMA [ * ] within ten (10)
days of the Effective Date by wire transfer of immediately available funds to an
account designated by XOMA.
6.2 SPACE FEE. Beginning with the calendar quarter commencing
[ * ] and until production of the first registration Batch at Commercial Scale
pursuant to Section 4.2(a), Onyx shall pay XOMA a dedicated space fee for the
Suite of [ * ] per calendar quarter, payable on a calendar quarterly basis in
advance by wire transfer of immediately available funds to an account designated
by XOMA. After the calendar quarter in which such first registration Batch is
supplied to Onyx, no further dedicated space fee shall be payable.
6.3 EQUIPMENT AND FACILITY REIMBURSEMENT. Onyx will reimburse XOMA
[ * ] of the cost of equipment purchased pursuant to Sections 3.2(a) or (b) and
of facility modifications made pursuant to Section 3.2(c) after receipt of each
invoice for such costs.
6.4 PERSONNEL COSTS.
(a) DEVELOPMENT PHASE. For work performed under this
Agreement by XOMA staff (including technical development, manufacturing,
operations, quality control, quality assurance, regulatory affairs, and other
appropriate staff) during the Development Phase, through the completion of the
first registration Batch pursuant to Section 4.2(a) but not beyond, and for any
technology transfer work pursuant to Section 7.1(a), Onyx shall pay [ * ] of
XOMA's fully burdened staffing costs, [ * ] (collectively, "FULLY BURDENED
STAFFING COSTS"). Onyx will pay such costs on a calendar quarterly basis in
arrears upon presentation of an invoice from XOMA with a summary of supporting
information from XOMA's project cost system.
(b) MANUFACTURING PHASE. After completion of the first
registration Batch pursuant to Section 4.2(a), XOMA will cover all costs for
ongoing manufacture of Drug Substance by the per-Batch charge (as calculated in
Section 6.6) for Batches of Drug Substance meeting the Specifications produced
at Commercial Scale.
(c) REGULATORY WORK. For work performed under this
Agreement by XOMA personnel to (a) prepare and submit regulatory filings to
enable Drug Substance manufactured and supplied by XOMA to Onyx to be used in
human clinical trials, (b) carry out process validation work in connection with
any potential or actual BLA filing for ONYX-015 products, (c) prepare BLAs and
other documentation appropriate for obtaining Regulatory Approvals for ONYX-015
products, and (d) cooperate with Onyx in the filing and ongoing support of such
BLAs, Onyx shall pay [ * ] of XOMA's Fully Burdened Staffing Costs. Onyx will
pay such costs on a calendar quarterly basis in arrears upon presentation of an
invoice with a summary of supporting information from XOMA's project cost
system.
(d) POST-TERMINATION OR -EXPIRATION TECHNOLOGY TRANSFER.
Onyx shall pay [ * ] of XOMA's Fully Burdened Staffing Costs for technology
transfer work pursuant to Section 7.1(b).
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
15.
6.5 MILESTONE PAYMENTS. Within thirty (30) days of the achievement
of each milestone set forth in this Section 6.5, Onyx will pay to XOMA the
applicable milestone payment by wire transfer of immediately available funds to
an account designated by XOMA. Other than milestones for additional Yield
improvements pursuant to Section 6.5(b), no milestone payment will be payable
more than once.
(a) INITIAL COMMERCIAL SCALE BATCH MEETING SPECIFICATIONS
AND WITH ADEQUATE YIELD. Upon production of the initial Batch at the [ * ]L
Commercial Scale in compliance with Specifications and cGMP with the required
minimum Yield pursuant to Section 4.2(a), Onyx will pay to XOMA a milestone
payment of [ * ].
(b) YIELD IMPROVEMENTS. For each increase of [ * ]
percentage points in manufacturing Yield in excess of [ * ] Yield (as such Yield
level may be adjusted pursuant to Section 4.2(a)), as calculated at the
completion of the first [ * ] Batches of Drug Substance at [ * ]L Commercial
Scale that comply with the warranties in Section 8.1(a) pursuant to Sections
4.2(a) and (b), Onyx will pay to XOMA a milestone payment of [ * ]. Increases in
Yield must be evidenced by the average Yield of the [ * ] Batches of Drug
Substance (or, if the Yield for one Batch differs by at least [ * ] percentage
points from the average Yield of the other [ * ] Batches, the average Yield of
such [ * ] Batches and the next Batch at Commercial Scale that complies with the
warranties in Section 8.1(a)) at or in excess of [ * ] Yield (as so adjusted).
For purposes of example:
If [ * ] consecutive Batches result in Yields of [ * ], respectively,
XOMA will have earned an aggregate milestone payment of [ * ], as there has been
a demonstrated Yield improvement of [ * ] percentage points, which is equal to
[ * ] increments of [ * ] percentage points so that XOMA would receive [ * ]
milestone payments of [ * ].
If [ * ] consecutive Batches result in Yields of [ * ], respectively,
and a [ * ] Batch results in a Yield of [ * ], the [ * ] Batch would be
disregarded, and XOMA will have earned an aggregate milestone payment of [ * ]
based upon the other [ * ] Batches, as there has been a demonstrated Yield
improvement of [ * ] percentage points, which is equal to [ * ] increments of
[ * ] percentage points so that XOMA would receive [ * ] milestone payments of
[ * ].
Milestone payments for Yield improvements under this Section 6.5(b)
shall be payable only once for each [ * ] percentage points of Yield
improvement.
(c) REGULATORY APPROVAL FOR FACILITY. Upon licensure by
the FDA of ONYX-015 for manufacture of Drug Substance by XOMA at the Facility,
Onyx will pay to XOMA a milestone payment of [ * ].
6.6 COMMERCIAL SCALE BATCH PAYMENTS.
(a) BATCH PRICE. For each Batch produced pursuant to
Sections 4.2(b), 5.2(a) or 5.2(b), Onyx will pay to XOMA an amount equal to
[ * ]. For clarity, Onyx shall not be obligated under this Section 6.6(a) to
pay for the Batch of Drug Substance produced by XOMA pursuant to Section
4.2(a), as Onyx will compensate XOMA for its facilities, materials and labor
costs for that Batch during the Development Phase pursuant to Sections 6.2
and 6.4.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
16.
(b) ADDITIONAL BATCHES. If Onyx requests pursuant to
Section 5.2(c) that XOMA manufacture additional Batches of Drug Substance in
addition to the minimum annual Batch commitment in Sections 5.2(b), XOMA will
charge Onyx for these additional Batches at [ * ] of XOMA's standard
manufacturing cost therefor, plus an amount equal to [ * ] of the difference
between [ * ] and [ * ] of such standard manufacturing costs (provided that such
number is equal to or less than [ * ]), but in no event will XOMA charge Onyx,
or Onyx be obligated to pay, any amounts for such Batches in excess of the
per-Batch charge to Onyx set forth in this Section 6.6(b), as adjusted pursuant
to Section 6.6(c).
For purposes of example:
If XOMA's standard manufacturing costs for an additional Batch were
[ * ], then Onyx would pay [ * ] for such Batch, calculated as follows: [ * ];
and
if XOMA's standard manufacturing costs for an additional Batch were
[ * ], then Onyx would pay [ * ] for such Batch, because [ * ], which exceeds
[ * ].
(c) ADJUSTMENTS. The per-Batch fee of [ * ], as adjusted
pursuant to this Section 6.6(c), may be increased annually beginning in calendar
year 2001 by the percentage increase in XOMA's costs for materials, salaries and
operations relating to manufacture of Drug Substance, relative to such costs in
effect for December 31, 2000, as shown by reasonably acceptable documentation,
up to a maximum of [ * ] in any one calendar year.
(d) ADDITIONAL ORDERS AT COMMERCIAL SCALE. After
Attainment of Commercial Scale, for each Batch of Drug Substance manufactured by
XOMA at Commercial Scale pursuant to Section 5.2 that, by the Parties' agreement
or by determination pursuant to Section 5.6(c), does not comply with XOMA's
warranties in Section 8.1(a), at Onyx's election the Parties will negotiate in
good faith to attempt to reach agreement on a price at which XOMA will sell such
Batch to Onyx for purposes other than use in humans.
6.7 PAYMENT. All payments to be made under this Agreement shall be
made in United States dollars in the United States to a bank account designated
by the party to be paid. Invoices shall be due and payable upon receipt, and all
properly invoiced amounts not paid within thirty (30) days of receipt of the
invoice shall accrue interest at a rate equal to the lesser of prime rate as
posted by Citibank, N.A., plus two percent (2%), or the highest interest rate
permitted under applicable law.
6.8 RECORDS. XOMA will keep accurate books and accounts of record
in connection with the manufacture, use and/or sale by it of Drug Substance
hereunder in sufficient detail to permit accurate determination of all figures
necessary for verification of payment obligations set forth in this Section 6.
Such records shall be maintained for a period of three (3) years (or for a
particular year upon notice from Onyx prior to the end of such 3 year period,
four (4) years) from the end of each year in which sales occurred or expenses
were incurred. Onyx, at its expense, through a certified public accountant,
shall have the right to access such books and records for
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
17.
the sole purpose of verifying the reports regarding amounts due; such access
shall be conducted after reasonable prior notice by Onyx during XOMA's normal
business hours and shall not be more frequent than once during each calendar
year. Said accountant shall not disclose to Onyx or any other party any
information except that which should properly be contained in an expense
report required under this Agreement. If such accounting determines that
XOMA's error resulted in Onyx paying more than properly due in respect of any
Batch or calendar quarter, then XOMA will promptly reimburse such amount, and
if the amount of such excess payment was at least five percent (5%) of the
amount properly due, XOMA will promptly reimburse Onyx for the costs of such
accounting (including the fees and expenses of the certified public
accountant). If such accounting determines that XOMA's error resulted in Onyx
paying less than properly due in respect of any Batch or calendar quarter,
then Onyx will promptly pay the amount of underpayment.
6.9 TAXES WITHHELD. Any income or other tax that one Party
hereunder, its Affiliates or sublicensees is required to withhold (the
"WITHHOLDING PARTY") and pay on behalf of the other Party hereunder (the
"WITHHELD PARTY") with respect to amounts payable under this Agreement shall be
deducted from and offset against said amounts prior to remittance to the
Withheld Party; PROVIDED, HOWEVER, that in regard to any tax so deducted, the
Withholding Party shall give or cause to be given to the Withheld Party such
assistance as may reasonably be necessary to enable the Withheld Party to claim
exemption therefrom or credit therefor, and in each case shall furnish the
Withheld Party proper evidence of the taxes paid on its behalf. The Withholding
Party shall comply with reasonable requests of the Withheld Party to take any
proper actions that may minimize such withholding obligation.
7. TECHNOLOGY AND INFORMATION.
7.1 TECHNOLOGY TRANSFER.
(a) PERIODIC UPDATES. On a calendar quarterly basis, each
Party will provide to the other Party written copies of all Project Innovations
known to the first Party not previously disclosed to the other Party. Onyx will
reimburse XOMA for the costs of XOMA representatives for such technology
transfer work pursuant to Section 6.4(a). Onyx shall be entitled to maintain and
use such documents within the scope of its license in Section 7.3(c) for itself,
its Affiliates, or Third Parties.
(b) EXPIRATION, TERMINATION OR UPON REQUEST. Upon
expiration or termination of this Agreement, or at any other time, at Onyx's
request XOMA will carry out the technical transfer to Onyx and/or Third Parties
designated by Onyx of the process and technology used to manufacture and test
Drug Substance under this Agreement. In connection with such technical transfer,
upon reasonable notice XOMA will permit reasonable access to the Suite during
normal business hours to representatives of Onyx or its Third Party designees
reasonably acceptable to XOMA to learn about the relevant process and
technology. Prior to obtaining access, such representatives will enter into
XOMA's standard form of confidentiality agreement, which will be commercially
reasonable and will permit such representatives to disclose information learned
to Onyx and such Third Party. Onyx will reimburse XOMA for the costs of XOMA
personnel for such technology transfer work pursuant to Section 6.4(d).
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
18.
7.2 INFORMATION.
(a) DOCUMENTATION. Each Party shall maintain, in
accordance with and for the period required under cGMP and all other applicable
laws, rules and regulations, complete and adequate records pertaining to the
methods and facilities used for the cGMP manufacture, processing, testing,
packing, labeling, holding and distribution of Drug Substance so that the
ONYX-015 products may be used in humans.
(b) ACCESS. Onyx shall have unrestricted access during
normal business hours to copies of Batch records and any other documentation
relating to manufacture of Drug Substance by XOMA under this Agreement and shall
be free, subject to Section 10, to copy and use such documentation as reasonably
required for any normal regulatory or business use relating to ONYX-015 or
ONYX-015 Derivatives.
(c) AUDIT OF RECORDS. No more than once per six (6)
months, unless otherwise required under applicable governmental law, rule,
regulation or order, upon at least thirty (30) days' advance request and during
normal business hours, Onyx shall have the right to inspect XOMA's records
relating to the manufacture of Drug Substance, including without limitation
manufacturing, quality control/quality assurance, and cost and financial
records.
7.3 LICENSES.
(a) DEVELOPMENT AND MANUFACTURING LICENSE TO XOMA. Onyx
hereby grants to XOMA a non-exclusive, royalty-free, paid-up, non-transferable,
non-sublicensable license to practice Onyx Innovations, in each case solely to
perform its obligations under this Agreement, under all Intellectual Property
Rights that Onyx Controls that, but for the grant of the license in this Section
7.3(a), would be infringed or misappropriated by XOMA's performance of such
obligations.
(b) PROJECT INNOVATIONS LICENSE TO XOMA. Subject to the
terms and conditions of this Agreement, Onyx hereby grants to XOMA a
non-exclusive, worldwide, royalty-free, paid-up, non-transferable (except for
sublicenses permitted under this Section 7.3(b)) license, which shall be
sublicensable only to Third Parties (i) who are XOMA's collaboration partners
(pursuant to a written agreement) for the development and/or commercialization
of products and (ii) the identity of whom XOMA has given prior written notice to
Onyx, to practice all Project Innovations at all XOMA facilities and the
facilities of such Third Parties for any purpose other than the research,
development, manufacture, or commercialization of any adenoviruses, under all
Intellectual Property Rights that Onyx Controls that, but for the grant of the
license in this Section 7.3(b), would be infringed or misappropriated by the
practice of Project Innovations in accordance with this Section 7.3(b).
(c) XOMA INNOVATIONS LICENSE TO ONYX. Subject to the
terms and conditions of this Agreement, XOMA hereby grants to Onyx a
non-exclusive, worldwide, royalty-free, paid-up, non-transferable (except for
assignments pursuant to Section 12.6 and sublicenses permitted under this
Section 7.3(c)) license, which shall be sublicensable only to Onyx Partners, to
make, have made, use, import, offer for sale, sell and otherwise practice all
XOMA Innovations used in the manufacture of ONYX-015 under this Agreement, only
for the
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
19.
purposes of researching, developing, manufacturing and commercializing
ONYX-015 and ONYX-015 Derivatives and products incorporating them, under all
Intellectual Property Rights that XOMA Controls that, but for the grant of
the license in this Section 7.3(c), would be infringed or misappropriated by
the manufacture, use, import, offer for sale, sale or other practice of such
XOMA Innovations in accordance with this Section 7.3(c).
7.4 OWNERSHIP OF INNOVATIONS AND INTELLECTUAL PROPERTY.
(a) THIRD PARTY TECHNOLOGY. Prior to the application to
the manufacturing process for Drug Substance of any Innovation that, to the
knowledge of any XOMA Project Team member, is proprietary to any Third Party,
XOMA will notify Onyx. If Onyx objects to the use of any such Innovation, XOMA
shall not apply it to such process.
(b) ONYX INNOVATIONS. Subject only to the licenses in
Section 7.3, Onyx shall retain all right, title and interest in and to all
Innovations that Onyx either Controls as of the Effective Date or gains Control
of independently of activities under this Agreement (collectively, "ONYX
INNOVATIONS"), and all Intellectual Property Rights arising therefrom.
(c) XOMA INNOVATIONS. Subject only to the licenses in
Section 7.3, XOMA shall retain all right, title and interest in and to all
Innovations that XOMA either Controls as of the Effective Date or gains Control
of independently of activities under this Agreement, and all Intellectual
Property Rights arising therefrom ("XOMA INNOVATIONS").
(d) PROJECT INNOVATIONS.
(i) All Innovations made, conceived, reduced to
practice, authored, or otherwise generated or developed in whole or in part in
the course of activities under this Agreement shall be "PROJECT INNOVATIONS".
Inventorship of discoveries or inventions included within Project Innovations
and authorship of works of authorship included within Project Innovations shall
be determined in accordance with the patent and copyright laws of the United
States of America, respectively.
(ii) Without further payment to XOMA, Onyx shall
own all right, title and interest in and to all Project Innovations, whether
made, conceived, reduced to practice, authored, or otherwise generated or
developed solely by XOMA personnel, solely by Onyx personnel, or jointly by XOMA
and Onyx personnel, and all Intellectual Property Rights arising therefrom. XOMA
will, and hereby does, assign to Onyx all of its right, title and interest in
and to Project Innovations and Intellectual Property Rights arising therefrom.
XOMA will provide reasonable assistance to Onyx, at Onyx's expense, in obtaining
and enforcing and defending Onyx's ownership of the Project Innovations and
appurtenant Intellectual Property Rights, including without limitation and as
applicable, the assignment to Onyx of all their right, title and interest of its
employees or independent contractors in and to such Project Innovations and
appurtenant Intellectual Property Rights.
7.5 PATENTING OF PROJECT INNOVATIONS. Onyx will have first right,
but not the obligation, to control the preparation, filing and prosecution of
Patents claiming Project Innovations and of maintenance of Patents issuing
thereon. Onyx will promptly provide XOMA with copies of Patents filed with any
governmental entity. With respect to any Project
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
20.
Innovation that is potentially patentable, XOMA may request in writing that
Onyx take specific, reasonable actions to (i) prepare, file or prosecute
Patents claiming such Project Innovation, in a particular country, (ii)
maintain any Patents issued that claim a Project Innovation, and/or (iii)
protect against abandonment of a Patent that claims a Project Innovation. If
such actions are not undertaken within sixty (60) days of Onyx's receipt of
such written request (or if sooner, such time as applicable patent rights
would be lost due to passage of time) and timely pursued thereafter, Onyx
will permit, and XOMA at its option and expense may undertake, such actions.
The Party not undertaking such actions shall reasonably cooperate with the
other Party at such other Party's cost and shall provide to the other Party
whatever assignments and other documents that may be needed in connection
therewith. The Party undertaking such actions will be fully responsible for
the costs and expenses of such actions.
7.6 INFRINGEMENT OF PATENTS.
(a) Each Party shall promptly notify the other Party of
any infringement, misappropriation or other unauthorized use of an Intellectual
Property Right licensed under this Agreement in the field of the development,
manufacture, use and/or sale of adenoviruses that comes to such Party's
attention. The notice shall set forth the facts of such infringement in
reasonable detail. Onyx shall have the sole right, but not the obligation, to
institute, prosecute, and control, at its expense, any action or proceeding
against the Third Party infringer of a Patent claiming a Project Innovation. If
Onyx institutes an action against such infringer, XOMA will give Onyx reasonable
assistance and authority to control, file, and prosecute the suit as necessary
at Onyx's expense. Onyx shall retain any damages or other monetary awards that
it recovers in pursuing any action under this Section 7.6(a).
(b) Each Party has the sole right to enforce any
Intellectual Property Rights that it Controls.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
21.
8. REPRESENTATIONS AND WARRANTIES; DISCLAIMERS.
8.1 DRUG SUBSTANCE WARRANTIES AND REMEDY.
(a) WARRANTIES. XOMA warrants that for any Batch of Drug
Substance delivered pursuant to Section 5.5: (i) XOMA will manufacture the Batch
in accordance with cGMP and other applicable laws and FDA and Regulatory
Authority rules and regulations; (ii) the Batch will conform to the
Specifications at the time of delivery pursuant to Section 5.5, (iii) such Batch
will not be adulterated or misbranded within the meaning of the FD&C Act, and
(iv) it is providing title to such Batch to Onyx free and clear of any
encumbrances. Onyx's sole remedies and XOMA's entire liability with respect to
this warranty are set forth in Sections 5.6, 8.1(b), and 9.2. The warranties in
this Section 8.1(a) are the only warranties made by XOMA with respect to Batches
delivered under this Agreement and may only be modified or amended by a written
instrument signed by a duly authorized officer of XOMA and accepted by Onyx.
(b) REMEDY. If any Batch delivered by XOMA pursuant to
Section 5.5 is not in compliance with the warranties in Section 8.1(a) and Onyx
properly rejects or revokes acceptance for such Batch pursuant to Section 5.6,
XOMA will, at Onyx's sole option, either (i) replace or rework such Batch as
promptly as reasonably practicable with no additional cost to Onyx, or, (ii) if
XOMA has acknowledged in writing that it is technically unable to produce Drug
Substance in conformity with then-current Specifications, XOMA will refund any
sums actually paid therefor by Onyx. The remedy of replacement or refund is
available only if such nonconformance was not caused by Onyx's neglect, improper
testing or improper storage, including without limitation storage at
inappropriate temperatures, transportation, use beyond any dating provided, by
accident, fire or other hazard.
8.2 GENERAL REPRESENTATIONS AND WARRANTIES. Each Party hereby
represents and warrants to the other Party that:
(a) CORPORATE EXISTENCE AND POWER. It is a corporation
(in the case of Onyx) or a limited liability company (in the case of XOMA) duly
organized, validly existing and in good standing under the laws of the state in
which it is incorporated or organized, as applicable, and has full corporate or
company power and authority and the legal right to own and operate its property
and assets and to carry on its business as it is now being conducted and as
contemplated in this Agreement, including, without limitation, the right to
grant the licenses granted hereunder.
(b) AUTHORITY AND BINDING AGREEMENT. As of the Effective
Date, (i) it has the corporate or company power and authority and the legal
right to enter into this Agreement and perform its obligations hereunder; (ii)
it has taken all necessary corporate or company action on its part required to
authorize the execution and delivery of the Agreement and the performance of its
obligations hereunder; and (iii) the Agreement has been duly executed and
delivered on behalf of such Party, and constitutes a legal, valid and binding
obligation of such Party and is enforceable against it in accordance with its
terms.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
22.
(c) TITLE. As of the Effective Date, it has sufficient
legal and/or beneficial title under its Intellectual Property Rights necessary
to perform activities contemplated under this Agreement and to grant the
licenses that it is obligated to grant under this Agreement.
8.3 WARRANTY DISCLAIMER. THE REPRESENTATIONS AND WARRANTIES IN
SECTIONS 8.1(a) AND 8.2 ARE IN LIEU OF ALL OTHER WARRANTIES, EXPRESS, IMPLIED,
OR STATUTORY, AND EACH PARTY EXPRESSLY DISCLAIMS ANY AND ALL OTHER WARRANTIES,
INCLUDING, WITHOUT LIMITATION, ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
PARTICULAR PURPOSE, NON-INFRINGEMENT, TITLE, CUSTOM OR TRADE.
9. INDEMNIFICATION; LIMITATION OF LIABILITY.
9.1 ONYX INDEMNITY. Onyx will indemnify, hold harmless and defend
XOMA and its Affiliates and their respective directors, officers, employees and
agents (the "XOMA INDEMNITEES") from and against any and all losses, claims,
suits, losses, damages, costs, fees and expenses (including without limitation
reasonable attorneys' fees) (collectively, "LOSSES") resulting from any Third
Party claim, demand, suit, action or proceeding ("THIRD PARTY CLAIM") to the
extent arising out of (a) any breach of Onyx's representations or warranties in
Section 8.2; (b) the Specifications; (c) the use (including without limitation
in human clinical trials), further manufacture or modification, transport,
storage, handling, possession, distribution, marketing, or disposal of the Drug
Substance after delivery by XOMA pursuant to Section 5.5, except for Drug
Substance that Onyx properly rejects or for which it properly revokes acceptance
pursuant to Section 5.6; (d) any infringement or misappropriation of Third Party
Intellectual Property Rights that is a result of the use or practice in
accordance with this Agreement of the manufacturing process for ONYX-015 as
transferred to XOMA pursuant to Section 4.1; or (e) any willful misconduct by
any Onyx Indemnitee with respect to Onyx's activities under this Agreement; in
each foregoing case provided both that XOMA provides Onyx with prompt notice of
any such Third Party Claim and the exclusive ability to defend (with the
reasonable cooperation of XOMA) or settle any such Third Party Claim and that
XOMA reasonably cooperates in the defense and/or settlement of such Third Party
Claim at Onyx's expense and request.
9.2 XOMA INDEMNITY. XOMA agrees to indemnify, hold harmless and
defend Onyx and its Affiliates and their respective directors, officers,
employees and agents (the "ONYX INDEMNITEES") from and against any and all
Losses resulting from any Third Party Claim to the extent arising out of (a) any
breach of XOMA's representations or warranties in Sections 8.1(a) or 8.2; (b)
XOMA's transportation, storage, use, handling or disposal of hazardous materials
used in or generated by XOMA's activities under this Agreement (excluding the
Drug Substance); (c) any personal injury arising from performance of this
Agreement by XOMA; or (d) any willful misconduct by any XOMA Indemnitee with
respect to XOMA's activities under this Agreement; in each foregoing case
provided both that Onyx provides XOMA with prompt notice of any such Third Party
Claim and the exclusive ability to defend (with the reasonable cooperation of
Onyx) or settle any such Third Party Claim and that Onyx reasonably cooperates
in the defense and/or settlement of such Third Party Claim at XOMA's expense and
request.
9.3 SEPARATE DEFENSES. If the Parties cannot agree as to the
application of Sections 9.1 and 9.2 to a particular Loss or Third Party Claim,
the Parties may conduct separate defenses of the relevant Third Party Claim.
Each Party further reserves the right to claim indemnity from
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
23.
the other Party in accordance with Sections 9.1 and 9.2 upon resolution of
the underlying Third Party Claim, notwithstanding the provisions of Sections
9.1 and 9.2 requiring the indemnified party to tender to the indemnifying
Party the exclusive ability to defend such Third Party Claim.
9.4 EXPENSES. Neither Party shall be required to pay over to
another party amounts called for under this Section 9 until the final resolution
of the Third Party Claim from which the right to such payment arose, except that
litigation costs, fees, and expenses will be paid in arrears on a calendar
quarterly basis, subject to reimbursement upon the agreement of the Parties or a
final determination by a court of competent jurisdiction that the indemnity
under this Section 9 did not apply to the Third Party Claim giving rise to such
costs, fees and expenses.
9.5 LIMITATION OF LIABILITY.
(a) IN NO EVENT SHALL EITHER PARTY OR ITS RESPECTIVE
AFFILIATES BE LIABLE FOR SPECIAL, EXEMPLARY, OR CONSEQUENTIAL OR PUNITIVE
DAMAGES, WHETHER IN CONTRACT, WARRANTY, TORT, STRICT LIABILITY, OR OTHERWISE,
EXCEPT FOR A WILLFUL FAILURE BY A PARTY OR ITS SUCCESSOR TO PERFORM IN
ACCORDANCE WITH THIS AGREEMENT, INCLUDING WITHOUT LIMITATION FOLLOWING ANY
CHANGE OF CONTROL OF SUCH PARTY.
(b) THE LIMITATIONS OF LIABILITY IN SECTION 9.5(A) ARE
INTENDED TO LIMIT THE LIABILITY OF THE APPLICABLE PARTY OR PARTIES AND SHALL
APPLY NOTWITHSTANDING ANY FAILURE OF ESSENTIAL PURPOSE OF ANY LIMITED REMEDY OR
WARRANTY. THE PARTIES HERETO ACKNOWLEDGE THAT THE TERMS OF THIS SECTION 9.5
REFLECT THE ALLOCATION OF RISK SET FORTH IN THIS AGREEMENT AND THAT THE PARTIES
WOULD NOT ENTER INTO THIS AGREEMENT WITHOUT THESE LIMITATIONS OF LIABILITY. THE
LIMITATIONS OF LIABILITIES UNDER THIS SECTION 9.5 SHALL NOT APPLY TO THE EXTENT
PROHIBITED BY APPLICABLE LAW.
10. CONFIDENTIALITY.
10.1 CONFIDENTIAL INFORMATION; EXCEPTIONS. Each Party will, and
will use commercially reasonable efforts to ensure that its employees will: (a)
maintain all Confidential Information of the other Party in trust and
confidence; (b) not disclose any Confidential Information of the other Party to
any Third Party (except that a Party may disclose such Confidential Information
to those of its employees, agents, independent contractors, Affiliates, or
sublicensees who require such information in order to perform under this
Agreement and who are subject to binding obligations of confidentiality and
limited use at least as restrictive as those of this Section 10); (c) not
disclose or use any Confidential Information of the other Party for any purposes
other than those necessary or permitted for performance under this Agreement;
(d) not use any Confidential Information of the other Party for any purpose or
in any manner that would constitute a violation of any applicable governmental
laws, rules, regulations, or orders, including without limitation the export
control laws of the United States; and (e) not reproduce any Confidential
Information of the other Party in any form except as required to perform in
accordance with this Agreement. Each Party will use at least the same standard
of care as it uses to protect its own Confidential Information of a similar
nature to prevent unauthorized disclosures or uses of Confidential Information
of the other Party, but in any event each Party will use no less than
commercially reasonable care to achieve such objectives. Each Party will
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
24.
promptly notify the other Party upon discovery of any unauthorized use or
disclosure of the Confidential Information of the other Party.
"CONFIDENTIAL INFORMATION" of a Party shall include all confidential or
proprietary information of such Party that the other Party receives or learns
under this Agreement. Confidential Information shall include without limitation
the manufacturing processes transferred to, used by or improved by XOMA under
this Agreement.
Confidential Information shall not include any information to the
extent that it:
(a) is now, or hereafter becomes, through no act or
failure to act on the part of the receiving Party in breach of this Section 10,
generally known or available;
(b) is known by the receiving Party at the time of
receiving such information, as shown by written records predating such receipt;
(c) is furnished after the Effective Date to the
receiving Party by a Third Party, without breach of and not subject to any
obligation of confidentiality; or
(d) is independently developed by the receiving Party
without use of or reference to Confidential Information of the other Party, as
shown by independent written records contemporaneous with such development.
The Parties agree that the material financial, commercial, scientific
and technical terms of the Agreement will be considered Confidential Information
of both Parties. Notwithstanding the foregoing, either Party may disclose such
terms to bona fide potential corporate partners, potential investors or merger
or acquisition partners, and to financial underwriters and legal and financial
advisors, provided that all such disclosures shall be made only to such Parties
under commercially reasonable obligations of confidentiality equivalent to the
obligations set forth in this Section 10.
10.2 AUTHORIZED DISCLOSURE. Notwithstanding any other provision of
this Agreement, each Party may disclose Confidential Information of the other
Party:
(a) to the extent and to the persons and entities
required by an applicable governmental law, rule, regulation or order; PROVIDED,
HOWEVER, that the receiving Party shall first have given prompt notice to the
other Party hereto as soon as reasonably practicable to enable it to seek any
available exemptions from or limitations on such disclosure requirement and
shall reasonably cooperate in such efforts by the other Party;
(b) to the extent and to the persons and entities
required by rules of the National Association of Securities Dealers;
(c) as necessary to file or prosecute patent
applications, prosecute or defend litigation or otherwise establish rights or
enforce obligations under this Agreement, but only to the extent that any such
disclosure is necessary;
(d) to permitted sublicensees under this Agreement; or
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
25.
(e) to Regulatory Authorities, for the purpose of
obtaining Regulatory Approval for ONYX-015; and
(f) to identified Third Parties with the prior, express,
specific, written permission of the disclosing Party.
10.3 PRESS RELEASES. Promptly after entering into this Agreement,
each Party will issue its own press release in the respective form attached
hereto as Exhibit C. Neither Party will issue any other publicity release or
announcement containing additional information beyond that in Exhibit C without
the advance written consent of the other Party, except as such release or
announcement may be required by law, in which case the Party making the release
or announcement shall, before making any such release or announcement, afford
the other Party a reasonable opportunity to review and comment upon such release
or announcement to the extent practicable.
10.4 REQUESTS FOR CONFIDENTIAL TREATMENT. The Parties acknowledge
that the rules and regulations promulgated by the U.S. Securities and Exchange
Commission ("SEC") will require that each Party disclose the non-confidential
material terms of this Agreement and file a copy hereof with the SEC. The
Parties will use commercially reasonable efforts to secure confidential
treatment under applicable laws, rules and regulations for financial, commercial
and scientific and technical terms that are trade secrets of either Party, will
agree, prior to submission to the SEC of a confidential treatment request
(without delaying the timeliness of such submission), upon the terms for which
each Party will seek confidential treatment, and will coordinate in good faith
with respect to any such requests and any responses to any SEC comments on or
responses to such requests, provided, however, that after using such efforts
each Party will be free to make disclosures that it reasonably believes are
required by applicable law, rule or regulation or that the SEC will otherwise
require.
10.5 RETURN OF CONFIDENTIAL INFORMATION. Upon any expiration or
termination of this Agreement, each Party will use diligent efforts (including
without limitation a diligent search of files and computer storage devices) to
return or destroy all Confidential Information of the other Party and all
copies, summaries, compilations, extracts or other derivatives thereof, except
to the extent such Confidential Information is necessary to exercise any license
or other right surviving termination of this Agreement. Additionally, each Party
will be allowed to keep one archival copy of any Confidential Information of the
other Party for record keeping purposes only.
10.6 INJUNCTIVE RELIEF. The Parties expressly acknowledge and
agree that any breach or threatened breach of this Section 10 may cause
immediate and irreparable harm to the Party whose Confidential Information is
at issue, which harm may not be adequately compensated by damages. Each Party
therefore agrees that in the event of such breach or threatened breach and in
addition to any remedies available at law, the Party whose Confidential
Information is at issue shall have the right to secure equitable and
injunctive relief, without bond, in connection with such a breach or
threatened breach.
10.7 SURVIVAL. The terms of this Section 10 shall survive for the
longer of (i) seven (7) years after expiration or termination of this Agreement
or (ii) ten (10) years from the Effective Date.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
26.
10.8 SUPERSEDING EFFECT. The provisions of this Section 10
supersede the existing Confidentiality Agreement between the Parties dated as of
October 19, 2000, and any information disclosed thereunder shall be deemed
"Confidential Information" under this Agreement.
11. TERM AND TERMINATION.
11.1 TERM. The initial term of this Agreement will commence on the
Effective Date and shall expire upon the fifth anniversary thereof. At its sole
option, Onyx may extend the term of this Agreement for successive three (3) year
periods upon at least [ * ] written notice (e.g., by notice given on or before
the [ * ] anniversary of the Effective Date, Onyx may extend the term of this
Agreement until the eighth anniversary of the Effective Date), PROVIDED,
HOWEVER, that Onyx may not extend the term beyond the effective date of any
termination by XOMA pursuant to Section 11.2.
11.2 TERMINATION BY XOMA.
(a) XOMA may terminate this Agreement at will effective
upon the earlier of (i) at least [ * ] months' prior written notice, or (ii) the
time, occurring after issuance by the FDA of a Regulatory Approval for the
ONYX-015 product, at which XOMA has completed the manufacture and supply to
Onyx, in accordance with this Agreement, of a number of Batches that is equal to
the minimum number of Batches that XOMA would be required to supply under
Section 5.2(b) during the portion of the term of this Agreement that remains
after the issuance of such Regulatory Approval (including any term extensions
pursuant to Section 11.1) or such greater number as the Parties agree, provided
that such supplied Batches have a Shelf Life that is commercially reasonable.
(b) XOMA may terminate this Agreement upon at least [ * ]
months' prior written notice if, within thirty (30) days of notice given by XOMA
pursuant to Section 3.3 hereof of its desire to use the Suite for another
product, Onyx does not elect to pay to XOMA the specified [ * ] fee.
11.3 TERMINATION BY ONYX.
(a) DELAY IN PERFORMANCE BY XOMA. If Onyx has not
materially breached its obligations to assist XOMA or enable XOMA's performance
under this Agreement, then Onyx may terminate this Agreement without penalty or
further obligation to XOMA (except as otherwise stated in this Section 11.3)
upon at least ninety (90) days prior written notice if:
(i) XOMA has not initiated manufacture of Drug
Substance (defined as thawing a vial of cells in preparation for manufacturing a
Batch of Drug Substance) in the Suite by [ * ];
(ii) XOMA has not manufactured and supplied to
Onyx or its designee a Batch of Drug Substance meeting the Specifications (as in
existence on the Effective Date) at the [ * ]L Development Scale (or greater
scale) by [ * ], provided that Onyx has not significantly delayed the timelines
for the Project due to Onyx's decisions based on changed needs for ONYX-015 for
clinical trials or on implementation of process changes;
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
27.
(iii) XOMA has not manufactured and supplied to
Onyx or its designee a Batch of Drug Substance at [ * ]L Commercial Scale
meeting the then-current Specifications by [ * ], provided that Onyx has not
significantly delayed the timelines for the Project due to Onyx's decisions
based on changed needs for ONYX-015 for clinical trials on implementation of
process changes; or
(iv) after the Attainment of Commercial Scale,
XOMA fails to successfully manufacture the number of Batches of Drug Substance
ordered by Onyx in compliance with its guaranteed minimum annual number of
Batches in any applicable twelve (12) month period under Section 5.2.
If Onyx's actions, inactions (e.g. Onyx's failure to provide raw
materials, etc., pursuant to Section 2.1(b)) or decisions cause a delay in
achievement of the target dates in this Section 11.3(a), Onyx and XOMA will in
good faith agree upon an extension of the target dates. If Onyx terminates this
Agreement pursuant to this Section 11.3(a), Onyx will reimburse XOMA for all
appropriate costs under this Agreement incurred by XOMA to the date of notice of
termination by Onyx for services performed, for commitments that cannot be
canceled, and for resources that cannot be reallocated, and for all other costs
that XOMA incurs in transferring the technology to Onyx or a Third Party at
Onyx's request pursuant to Section 7.1(b). XOMA will use diligent, commercially
reasonable efforts to minimize any costs or obligations that cannot be canceled
and to reallocate any resources that were dedicated to the Project.
(b) FOR CONVENIENCE BEFORE ATTAINMENT OF COMMERCIAL
SCALE. Prior to Attainment of Commercial Scale, Onyx may terminate this
Agreement by giving XOMA at least one-hundred twenty (120) days' prior notice
and making a payment to XOMA of [ * ]. In addition, Onyx will reimburse XOMA for
all appropriate costs under this Agreement incurred by XOMA to the effective
date of termination for services performed, for commitments that cannot be
canceled, and for resources and materials on hand that cannot be reallocated,
and for all other costs that XOMA incurs in transferring the technology to Onyx
or a Third Party at Onyx's request pursuant to Section 7.1(b).
(c) FOR CONVENIENCE AFTER ATTAINMENT OF COMMERCIAL SCALE.
(i) Onyx may terminate this Agreement for
convenience upon written notice at any time after the Attainment of Commercial
Scale. If termination is not then permitted under either Sections 11.3(a)(iv) or
11.4, then any such termination by Onyx after Attainment of Commercial Scale
shall be a termination under this section 11.3(c).
(ii) With its termination notice under Section
11.3(c)(i), Onyx may propose to XOMA the substitution of another product for the
ONYX-015 product, and in this event the Parties agree to negotiate diligently
and in good faith to revise this Agreement so that XOMA would manufacture and
supply the bulk form of the alternate product instead of Drug Substance, in such
as way as to provide comparable economic benefit to XOMA as would have been
derived by XOMA in the initial Agreement.
(iii) If the Parties are unable to reach a revised
Agreement pursuant to Section 11.3(c)(ii) within one-hundred twenty (120) days
of Onyx's initial notice, this
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
28.
Agreement shall terminate and Onyx shall pay to XOMA a termination fee of
[ * ] of the cost for commercial Batches as calculated pursuant to Section
6.6, for the guaranteed minimum number of Batches that Onyx would have been
obligated to order pursuant to Section 5.2 during the fifteen (15) months
following the date of the notice of termination, based on remaining order
obligations during the current twelve (12) month period during which
termination occurs and order obligations calculated on a pro rata basis for
the portion of the fifteen (15) month period following such current twelve
(12) month period.
For purposes of example, if Onyx were to terminate 18 months after the
Attainment of Commercial Scale after having ordered [ * ] Batches during the 12
month period following the first anniversary of the Attainment of Commercial
Scale, then during the ensuing 15 months, Onyx would have been obligated to
order [ * ] Batches during the remaining 6 months of the current 12 month period
and during the first 9 months of the ensuing 12 month period, Onyx's pro rata
Batch order obligation would be equal to (9 months/12 months)x([ * ] Batch
minimum obligation for 12 month period), or [ * ] batches. Based on an order
obligation of [ * ] total Batches and a Batch price of [ * ], under Section
11.3(c)(iii) Onyx would be obligated to pay XOMA [ * ], which represents [ * ]
of the payments for the [ * ] Batches at Commercial Scale.
11.4 BREACH. If a Party materially breaches this Agreement, (i) and
such breach is reasonably curable within thirty (30) days, then the other Party
may terminate this Agreement upon thirty (30) days prior written notice to the
first Party specifying such breach if the breaching Party fails to cure the
breach within such thirty (30) day period, or (ii) and such breach is not
reasonably curable within thirty (30) days, the other Party may give the
breaching Party written notice specifying such breach and may then terminate
this Agreement upon an additional twenty (20) days written notice if the
breaching Party either fails to provide by the end of the initial thirty (30)
day period a reasonable written plan to cure such breach as promptly as
reasonably practicable or fails to carry out such plan diligently and cure such
breach.
11.5 TECHNOLOGY TRANSFER. Upon any expiration or termination of
this Agreement, upon Onyx's request XOMA will, pursuant to Section 7.1(b),
transfer the technology used to manufacture and test ONYX-015 under this
Agreement to Onyx and/or Third Parties designated by Onyx at Onyx's cost, as set
forth in Section 6.4(d).
11.6 SURVIVING OBLIGATIONS. Termination or expiration of this
Agreement shall not affect any rights or obligations of either Party which may
have accrued up to the effective date of such termination or expiration. The
provisions of Sections 2.8, 3.2(a) (solely with respect to the last sentence in
such section), 5.9, 6.7, 6.8, 6.9, 7.1(b), 7.3(b), 7.3(c), 7.4(b), 7.4(c),
7.4(d), 7.5, 7.6 (solely with respect to the final three sentences in such
section), 8.1, 8.3, 9, 10, 11.5, 11.6 and 12 shall survive the termination or
expiration of this Agreement.
12. MISCELLANEOUS.
12.1 NOTICE. All notices hereunder shall be in writing and shall be
deemed given upon (i) personal delivery, (ii) facsimile transmission with
electronic confirmation of transmission, if sent during the recipient's normal
business hours, or otherwise on the recipient's next normal business day, (iii)
receipt after delivery by nationally-recognized bonded courier when sent for
next business day delivery, or (iv) receipt after sending by certified or
registered mail, postage
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
29.
prepaid and return receipt requested personally, to the following addresses
or fax numbers of the respective Parties:
If to XOMA: With a copy to:
XOMA (US) LLC Xxxxxx Xxxxxx & Xxxxxxx
0000 Xxxxxxx Xxxxxx Eighty Pine Street
Berkeley, CA 94710 Xxx Xxxx, XX 00000
Attention: Legal Department Attention: Xxxxxxxx X. Xxxxxxxx, Esq.
Fax No.: (000) 000-0000 Fax No.: (000) 000-0000
If to Onyx: With a copy to:
Onyx Pharmaceuticals, Inc. Cooley Godward LLP
0000 Xxxxxxxx Xxxxx Xxxx Xxxx Xxxx Xxxxxx
Xxxxxxxx, XX 00000 0000 Xx Xxxxxx Xxxx
Attention: CEO Xxxx Xxxx, XX 00000-0000
Fax No.: (000) 000-0000 Attention: Xxxxxx X. Xxxxx, Esq.
Fax No.: (000) 000-0000
A Party may change its address or fax number for notice by giving
notice under this Section 12.1.
12.2 USE OF NAMES. Neither Party shall use the name, trade name,
trademark, or other designation of the other Party (including contraction,
abbreviation or simulation of any of the foregoing) in advertising, publicity,
or other promotional activities. Under no circumstances shall either Party state
or imply in any promotional material, publication or other published
announcement that the other Party has tested or approved any product.
12.3 FORMAL DISPUTE RESOLUTION.
(a) ARBITRATION.
(i) Upon failure to resolve any claim, dispute,
or controversy of whatever nature arising out of or relating to this Agreement,
including, without limitation, any action or claim based on tort, contract, or
statute (including any claims of breach or violation of statutory or common law
protections from discrimination, harassment and hostile working environment), or
concerning the interpretation, effect, termination, validity, performance and/or
breach of this Agreement ("CLAIM"), using the dispute resolution procedure
described in Section 2.4, such Claim (other than one relating to the validity,
enforceability, infringement or misappropriation of an Intellectual Property
Rights) shall be resolved by final and binding arbitration ("ARBITRATION")
before a single arbitrator (or, at the election of either or both Parties, a
panel of three (3) arbitrators) ("ARBITRATOR") selected and administered by JAMS
("ADMINISTRATOR") in accordance with its then existing arbitration rules or
procedures regarding commercial or business disputes. Such arbitration shall
take place in San Francisco, California in the English language.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
30.
(ii) The provisions of California Code of
Civil Procedure sections 1283.05 and 1283.1 or their successor sections are
incorporated in and made a part of this Agreement. Depositions may be taken
and full discovery may be obtained in any arbitration commenced under this
Section 12.3(a).
(iii) The Arbitrator shall, within fifteen (15)
calendar days after the conclusion of the Arbitration hearing, issue a
written award and statement of decision describing the essential findings and
conclusions on which the award is based, including the calculation of any
damages awarded. The Arbitrator shall be authorized to award compensatory
damages, but shall NOT be authorized (i) to award non-economic damages, such
as for emotional distress, pain and suffering or loss of consortium, (ii) to
award punitive damages, or (iii) to reform, modify or materially change this
Agreement or any other agreements contemplated hereunder; PROVIDED, HOWEVER,
that the damage limitations described in parts (i) and (ii) of this sentence
will not apply if such damages are statutorily imposed. The Arbitrator also
shall be authorized to grant any temporary, preliminary or permanent
equitable remedy or relief he or she deems just and equitable and within the
scope of this Agreement, including, without limitation, an injunction or
order for specific performance.
(iv) Each Party shall bear its own attorneys'
fees, costs, and disbursements arising out of the arbitration, and shall pay
an equal share of the fees and costs of the Administrator and the Arbitrator;
PROVIDED, HOWEVER, the Arbitrator shall be authorized to, and must use best
efforts to designate one Party as the prevailing party, and upon any such
designation, must award to that prevailing Party reimbursement for its
reasonable attorneys' fees, costs and disbursements (including, for example,
expert witness fees and expenses, photocopy charges, travel expenses, etc.),
and/or the fees and costs of the Administrator and the Arbitrator. Absent the
filing of an application to correct or vacate the arbitration award under
California Code of Civil Procedure sections 1285 through 1288.8, each Party
shall fully perform and satisfy the arbitration award within fifteen (15)
days of the service of the award.
(v) BY AGREEING TO THIS BINDING ARBITRATION
PROVISION, THE PARTIES UNDERSTAND THAT THEY ARE WAIVING CERTAIN RIGHTS AND
PROTECTIONS WHICH MAY OTHERWISE BE AVAILABLE IF A CLAIM BETWEEN THE PARTIES
WERE DETERMINED BY LITIGATION IN COURT, INCLUDING, WITHOUT LIMITATION, THE
RIGHT TO SEEK OR OBTAIN CERTAIN TYPES OF DAMAGES PRECLUDED BY THIS PROVISION,
THE RIGHT TO A JURY TRIAL, CERTAIN RIGHTS OF APPEAL, AND A RIGHT TO INVOKE
FORMAL RULES OF PROCEDURE AND EVIDENCE.
(b) INTELLECTUAL PROPERTY DISPUTES. The Parties will
submit any Claim, relating to the validity, enforceability, infringement, or
misappropriation of any Intellectual Property Right that has not been
resolved pursuant to Section 2.4 to a court of competent jurisdiction.
12.4 RIGHTS IN BANKRUPTCY. All rights and licenses granted under
or pursuant to this Agreement are, and shall otherwise be deemed to be, for
purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to
"intellectual property" as defined under Section 101 of the U.S. Bankruptcy
Code. The Parties agree that Onyx, as a licensee under Section 7.3(c) and a
transferee under Sections 7.1 and 7.4(d) of such intellectual property rights
under this Agreement, and XOMA, as a licensee under Section 7.3(b), each
shall retain and may fully
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
31.
exercise all of its rights and elections under the U.S. Bankruptcy Code;
however, nothing herein shall be deemed to constitute a present exercise of
such rights and elections. The Parties further agree that, in the event of
the commencement of a bankruptcy proceeding by or against a Party under the
U.S. Bankruptcy Code, the other Party shall be entitled to a complete
duplicate of (or complete access to, as appropriate) any such intellectual
property as to which it is a licensee or transferee and all embodiments of
such intellectual property, and same, if not already in its possession, shall
be promptly delivered to such other Party (a) upon any such commencement of a
bankruptcy proceeding upon such other Party's written request therefore,
unless the first Party elects to continue to perform all of its obligations
under this Agreement, or (b) if not delivered under (a) above, upon rejection
of this Agreement by or on behalf of the first Party upon written request
therefor by the other Party.
12.5 WAIVER. The failure on the part of Onyx or XOMA to exercise
or enforce any rights conferred upon it hereunder shall not be deemed to be a
waiver of any such rights nor operate to bar the exercise or enforcement
thereof at any time or times hereafter.
12.6 ASSIGNMENT; BINDING EFFECT. Neither Party will assign its
rights or duties under this Agreement to another without the prior express
written consent of the other Party, which shall not be unreasonably withheld;
PROVIDED, HOWEVER, that
(a) either Party may assign this Agreement to a
successor by merger, acquisition, or sale of all or substantially all of such
Party's business assets in the field to which this Agreement relates, without
the other Party's consent, provided that such successor will expressly assume
in writing the obligation to perform in accordance with the terms and
conditions of this Agreement; and
(b) Onyx shall have the right to assign this Agreement
in its entirety (i) to Pfizer without the consent of XOMA or (ii) to any
other Onyx Partner with the prior written consent of XOMA, not to be
unreasonably withheld.
Any purported assignment not in compliance with this Section 12.5
shall be void. This Agreement shall be binding upon each Party's successors
and permitted assignees.
12.7 INDEPENDENT PARTIES. Neither Party is an employee or a
legal representative of the other Party for any purpose. Neither Party shall
have the authority to enter into any contracts in the name of or on behalf of
the other Party.
12.8 FORCE MAJEURE. Neither Party shall be liable to the other
for its failure to perform any of its obligations under this Agreement,
except for payment obligations, during any period in which such performance
is delayed because rendered impracticable or impossible due to circumstances
beyond its reasonable control, including without limitation earthquakes,
governmental regulation, fire, flood, labor difficulties, interruption of
supply of key raw materials, civil disorder, and acts of God, provided that
the Party experiencing the delay promptly notifies the other Party of the
delay and uses and continues to use commercially reasonable efforts to
overcome such delay.
12.9 SEVERABILITY. If any item or provision of this Agreement
shall to any extent be invalid or unenforceable, it shall be severed from
this Agreement, and the remainder of this
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
32.
Agreement shall not be affected thereby, and each term and provision of this
Agreement shall be valid and shall be enforced to the fullest extent
permitted by law.
12.10 GOVERNING LAW. This Agreement shall be governed and
construed in accordance with the laws of the State of California, except for
its principles of choice of law.
12.11 ENTIRE AGREEMENT; MODIFICATION. This Agreement, including
all Exhibits referenced herein, constitutes the entire agreement and
understanding of the parties and supersedes any prior agreements or
understandings relating to the subject matter hereof, except that with
respect to the Letter Agreement, the payment provisions shall remain in
effect but the term sheet attached thereto is hereby superseded. Any
modification of this Agreement shall be effective only to the extent it is
reduced to writing and signed by all parties.
12.12 COUNTERPARTS. This Agreement may be executed in
counterparts with the same force and effect as if each of the signatories had
executed the same instrument.
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-B2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
33.
IN WITNESS WHEREOF, each Party hereto has caused this Agreement to
be signed and delivered by its duly authorized officer or representative as
of the Effective Date.
ONYX PHARMACEUTICALS, INC. XOMA (US) LLC
By: /s/ HOLLINGS C. RENTON By: /s/ XXXXXXXX X. XXXXXX
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Name: Hollings C. Renton Name: Xxxxxxxx X. Xxxxxx
Title: Chief Executive Officer Title: Senior Vice President, Operations
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1934, AS AMENDED.
34.
EXHIBIT A
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EXHIBIT B
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EXHIBIT C
PRESS RELEASES
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XOMA CONTACTS INVESTOR RELATIONS CONTACTS MEDIA CONTACTS
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Xxxxx X. Xxxxx Xxxxxxx/Xxxxxxxxx & Associates Xxxxxx Xxxxxxxxx (Xxxxxx@xxxx.xxx)
Xxxxx X. Xxxxxx Xxxxx Xxxx (xxxxx@xxxx.xxx) Xxxxxx Xxxxx
(000) 000-0000 Xxxxxx Xxxxxxx (Xxxxxx@xxxx.xxx)
xxx.xxxx.xxx (xxxxxx@xxxx.xxx) (000) 000-0000
(000) 000-0000 xxx.xxxx.xxx
ONYX AND XOMA ESTABLISH STRATEGIC PROCESS DEVELOPMENT AND MANUFACTURING
RELATIONSHIP
BERKELEY, CA -- JANUARY 29, 2001 - Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX)
and XOMA Ltd. (Nasdaq: XOMA) today announced that they have agreed to a
strategic process development and manufacturing relationship under which XOMA
will scale-up production to commercial volume and manufacture Onyx's CI-1042
(also known as ONYX-015), a therapeutic product to treat cancer. CI-1042,
which is being developed in collaboration with Pfizer Inc., is currently in
Phase III testing for head and neck cancer.
The initial term of the agreement will be for five years, with options to
extend for additional three-year periods. XOMA will produce material for use
in clinical testing as well as for commercial sales upon approval. As part of
its development commitment XOMA will increase the fermentation volume to
commercial scale, improve the purification process, and seek FDA licensure of
its manufacturing facility for CI-1042. While dependent on the pace and
outcome of clinical trials, regulatory approvals, sales volume and other
factors, the financial scope of the agreement during the initial five-year
period is projected to exceed $35 million.
"I'm pleased to be embarking upon this relationship with Onyx," said Xxxx
Xxxxxxxx, Chairman, President, and CEO of XOMA. "It allows XOMA to further
leverage the core manufacturing and development competencies that attracted
the anti-CD11a collaboration with Genentech, and gives us an economic
interest in a promising late-stage cancer therapeutic. Our objective is to
have a financially attractive relationship from XOMA's perspective while at
the same time delivering substantial value to Onyx. This agreement further
validates our development and manufacturing strategy by showing a need for
our expertise within the biotechnology industry."
"We believe that XOMA can move quickly to scale-up production of CI-1042 to
increase the supply of CI-1042 for our various clinical trials as well as for
commercial launch of the product," said Hollings C. Renton, Chairman of the
Board, President and Chief Executive Officer of Onyx, "XOMA's manufacturing
and development support will enable us to focus our resources on accelerating
the clinical development program for this product."
Onyx Pharmaceuticals is engaged in the discovery and development of novel
targeted, highly selective cancer therapies. Based on its proprietary virus
technologies, the company is developing CI-1042 as its lead product. CI-1042
is a therapeutic tumor-selective, modified adenovirus (similar to the common
cold virus) that has been genetically engineered to replicate in and lyse
(burst) cancer cells that have abnormal p53 pathway function while sparing
normal
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
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cells that have functioning p53. Derangements in the p53 protein pathway are
the most common genetic abnormalities in human cancer. CI-1042 is currently
in a Phase III clinical trial for head and neck cancer and in Phase I and II
clinical trials for a number of additional cancer indications.
XOMA develops and manufactures antibody and other protein biopharmaceuticals
for disease targets that include immunological and inflammatory disorders,
infectious diseases and cancer. Late-stage programs include a collaboration
with Genentech, Inc. to develop the anti-CD11a antibody product for psoriasis
(Phase III) and kidney transplant rejection (Phase I/II), and an agreement
with the Xxxxxx Immuno Division of Xxxxxx Healthcare Corporation to develop
NEUPREX-Registered Trademark- (a systemic formulation of rBPI-21) for multiple
indications. Earlier stage products include: ING-1, a Human Engineered-TM-
antibody in Phase I studies for cancer; Genimune-TM-, a Human Engineered-TM-
antibody-based immunofusion product in preclinical development for autoimmune
diseases and immunological cancers; Mycoprex-TM-, a compound in preclinical
development for the treatment of fungal infections; and antiangiogenic
compounds for retinal disorders. For more information about XOMA's pipeline
and activities, please visit XOMA's web site at xxx.xxxx.xxx.
Statements made in this news release related to collaborative agreements and
current plans for product development, or that otherwise relate to future
periods, are forward-looking statements within the meaning of Section 27A of
the Securities Act of 1933 and Section 21E of the Securities Exchange Act of
1934. These statements are based on assumptions that may not prove accurate.
Actual results could differ materially from those anticipated due to certain
risks inherent in the biotechnology industry and for companies engaged in the
development of new products in a regulated market. These risks, including
those related to changes in the status of the Company's collaborative
relationships, the timing or results of pending or future clinical trials,
market demand for products, and marketing obligations of the collaborators
and other partners, actions by the Food and Drug Administration or the U.S.
Patent and Trademark Office, and uncertainties regarding the status of
biotechnology patents, are discussed in the Company's most recent annual
report on Form 10-K and in other SEC filings. Consider such risks carefully
in evaluating XOMA's prospects.
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BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
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[LOGO]
Contacts: Xxxxx X. Xxx Xxx Xxxxx or Xxxxx Xxxx
Onyx Pharmaceuticals, Inc. WeissComm
000-000-0000 000-000-0000
FOR IMMEDIATE RELEASE
ONYX AND XOMA ANNOUNCE STRATEGIC PROCESS DEVELOPMENT AND MANUFACTURING
AGREEMENT
RICHMOND, CALIF. (JANUARY 29, 2001) -- Onyx Pharmaceuticals, Inc. (Nasdaq:
ONXX) today announced that it has entered into a strategic process
development and manufacturing relationship with XOMA (US) LLC (Nasdaq: XOMA)
of Berkeley, California. Under the terms of the multi-year agreement, XOMA
will develop a large-scale process and will manufacture CI-1042 (ONYX-015)
for clinical trials and large-scale production. In return, Onyx will provide
XOMA with an upfront payment; support for development efforts on the process
scale up and production of bulk drug materials; and milestone payments
associated with attainment of large-scale production.
"We are delighted to have the opportunity to work with XOMA, one of the most
experienced companies in process development and large scale manufacturing of
biopharmaceuticals," said Hollings C. Renton, Chairman of the Board,
President and Chief Executive Officer of Onyx Pharmaceuticals, Inc. "The
agreement allows us to increase the supply of CI-1042 for our various
clinical trials and for commercial launch of CI-1042 under our collaboration
with Pfizer. XOMA will develop a large-scale manufacturing process for
CI-1042 based on our current process".
"We are looking forward to this opportunity to work with Onyx on their
innovative viral therapy for cancer," said Xxxx Xxxxxxxx, Chairman of the
Board, President and CEO of XOMA. "With
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BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
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XOMA's experience and infrastructure, we believe we can move quickly to
scale-up production of CI-1042, to enhance the manufacturability, and cost
structure of the product."
CI-1042 is a tumor-selective, modified adenovirus (a type of virus that can
cause a common cold) that has been genetically engineered to replicate in and
lyse (burst) cancer cells that have abnormal p53 pathway while sparing normal
cells which have (functioning) p53 protein. P53, a protein that protects the
cell from developing into a tumor cell, is the most commonly altered gene in
human cancer. CI-1042 is being jointly developed by Onyx Pharmaceuticals and
Pfizer Inc under an agreement signed in October 1999.
CI-1042, now in a Phase III clinical trial and various Phase I/II trials, is
currently being manufactured using a small-scale process. Due to the
limitation of the scale and the ability to produce less than sufficient
quantities of materials for multiple clinical trials, Onyx and Pfizer have
had to prioritize which clinical trials receive materials. The Phase II
clinical trials where the drug is administered intravenously received a
preferential supply of materials over the Phase III clinical trial. As a
result, the accrual of clinical sites and the enrollment of patients in the
Phase III study in recurrent Head and Neck cancer had been slowed. To date,
drug supplies have been available to two clinical sites. Currently, there are
10 clinical sites open for patient enrollment.
"Our current contract manufacturers have implemented plans to increase the
supplies of CI-1042, " said Hollings C. Renton. "With these actions and the
new support from XOMA, we believe that we can increase the accrual of the
clinical trials in an attempt to minimize any potential delay in timelines to
launch."
Onyx Pharmaceuticals is engaged in the discovery and development of novel
cancer therapies. Based on our proprietary virus technologies, we are
developing our lead product, CI-1042. CI-1042 is currently in a Phase III
clinical trial for head and neck cancer and in Phase I and II clinical trials
for a number of additional cancer indications. For more information about
CI-1042 and Onyx's pipeline and activities, visit Onyx Web site at
xxx.xxxx-xxxxx.xxx.
XOMA develops and manufactures antibody and other protein biopharmaceuticals
for disease targets that include immunological and inflammatory disorders,
infectious diseases and cancer. Late-stage programs include collaboration
with Genentech, Inc. to develop the anti-CD11a
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
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antibody product for psoriasis (Phase III) and kidney transplant rejection
(Phase I/II), and an agreement with the Xxxxxx Immuno Division of Xxxxxx
Healthcare Corporation to develop NEUPREX-Registered Trademark- (a systemic
formulation of rBPI21) for multiple indications. Earlier stage products
include ING-1, Genimune -TM-, Mycoprex -TM-, and antiangiogenic compounds.
For more information about XOMA's pipeline and activities, visit XOMA's web
site at xxx.xxxx.xxx.
This press release contains certain forward-looking statements regarding the
development of potential human therapeutic products that involve a number of
risks and uncertainties. Actual events may differ from the company's
expectations. In addition to the matters described in this press release, the
timeline for clinical activity, results of pending or future clinical trials,
and changes in the status of the company's collaborative relationships, as
well as the risk factors listed from time to time in the company's periodic
reports with the Securities and Exchange Commission, including but not
limited to its Annual Report on Form 10-K, may affect the actual results
achieved by the company.
[ * ]=CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24-b2 OF THE SECURITIES EXCHANGE ACT OF
1934, AS AMENDED.
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