Exhibit 99.1
CERTAIN PORTIONS OF THIS EXHIBIT HAVE BEEN OMITTED AND SUCH PORTIONS HAVE BEEN
FILED SEPARATELY WITH THE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.
RESEARCH AND DEVELOPMENT AGREEMENT
THIS AGREEMENT, made effective this 1st day of June, 1998 by and among the
PHARMACEUTICAL RESEARCH INSTITUTE of Xxxxxxx-Xxxxx Squibb Company, a Delaware
corporation, Xxxxx 000 & Xxxxxxxxxxxx Xxxx, Xxxxxxxxx, Xxx Xxxxxx 00000 ("BMS")
and NEOSE TECHNOLOGIES, INC., 000 Xxxxxx Xxxx, Xxxxxxx, Xxxxxxxxxxxx 00000
("NTI")
WITNESSETH
WHEREAS, BMS is engaged in the research, development, manufacture and sale
of pharmaceutical products, and
WHEREAS NTI has skill and expertise in research, development and production
of hetero-oligosaccharides, and
WHEREAS, BMS desires NTI to engage in a research and development project
which will result in the production of certain quantities of specific
hetero-oligosaccharides and new technology associated therewith;
NOW, THEREFORE, BMS and NTI intending to be legally bound, have agreed as
follows:
Article 1 - The Project
1.1 NTI agrees to produce and supply to BMS (a) [*] of ganglioside GM2; and
(b) [*] ganglioside GD2 in accordance with the prices and timetables get forth
in Appendix A attached herewith and fully incorporated herein. NTI further
agrees to supply to BMS at no charge all quantities of gangliosides GMS and GD2
prepared in the course of process optimization trials
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[*] We are seeking confidential treatment of these terms, which have been
omitted. The confidential portion has been filed separately with the Securities
and Exchange Commission.
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conducted prior to delivery of the aforementioned [*] quantities except that NTI
may retain such quantities of GMS and GD2 as are necessary for the maintenance
of standards, analytical testing and quality control. After delivery of the mg
quantities specified herein, NTI and BMS will mutually develop quality targets
and/or specifications.
1.2 NTI agrees to produce and thereafter to supply BMS with (a) [*] of
ganglioside GM2; and (b) up to [*] of ganglioside GD2 (total GD2 requirement to
be defined by BMS prior to its manufacture being initiated by NTI). These
quantities of ganglioside will be manufactured under GMP conditions, unless NTI
is otherwise instruction by BMS, in accordance with the timetable set forth in
Appendix A. These quantities of ganglioside will also be manufactured to meet
all quality targets and/or specifications as mutually agreed to by BMS and NTI
in accordance with Article 1.1 hereinabove.
1.3 Articles 1.1 and 1.2 taken together and in their entirety shall
hereinafter be referred to as the "PROJECT."
1.4 NTI agrees to commence work on the PROJECT upon the effective dat of
this Agreement, which shall be the first date written hereinabove (the
"Effective Date") and to use its best efforts to expeditiously complete the
PROJECT within the timetables set forth in Appendix A.
1.5 NTI acknowledges that all quantities of gangliosides GM2 and GD2
produced by NTI under the terms of this Agreement are the exclusive property of
BMS and may be used by BMS for any legitimate business purpose within the Field
(as defined in Article 9.3 of this Agreement) subject to the provisions of
Article 9 of this Agreement. In the event NTI produces any quantities of GMS or
GD2 materials in excess of quantities set forth in this Agreement, NTI shall
either transfer any and all such excess quantities to BMS based on the prices
set forth in Appendix A or, alternatively, at the sole discretion of BMS, NTI
shall destroy any and all of such excess quantities of GM2 and GD2 materials.
1.6 NTI agrees to perform all activities connected with the PROJECT in
accordance with all applicable laws, rules, regulations or other requirements of
local, state and federal governmental authorities.
1.7 With regard to any and all GMS and GD2 materials delivered to BMS by
NTI under the terms of this Agreement, NTI MAKES NO REPRESENTATIONS AND EXTENDS
NO WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED WITH RESPECT TO THE
SUITABILITY OF GM2 AND GD2 MATERIALS FOR ANY PARTICULAR PURPOSE OR USE AND NTI
EXPRESSLY DISCLAIMS ALL IMPLIED WARRANTIES OF
[ ] We are seeking confidential treatment of these terms, which have been
omitted. The confidential portion has been filed separately with the Securities
and Exchange Commission.
2
MERCHANTABILITY AND OF FITNESS FOR ANY PARTICULAR PURPOSE OR USE OF GM2 AND GD2
MATERIALS BY BMS.
Article 2 - Compensation
2.1 In consideration of the research and development services provided by
NTI in connection with the PROJECT and the quantities of GM2 and GD2 material
provided by NTI to BMS hereunder, BMS shall pay to NTI the amounts set forth in
Appendix A in accordance with the payment schedule therein.
2.2 In the event the PROJECT is canceled prior to completion by any early
termination of this Agreement pursuant to the terms of Article 7, NTI shall
receive payment from BMS adjusted to an amount equal to the pro rata portion of
work performed by NTI in accordance with Appendix A.
2.3 All payments made by BMS to NTI hereunder shall be by BMS corporate
check forwarded to:
NEOSE Technologies, Inc.
C/o Xxxxxxx Xxxxxx
Director, Business Development
000 Xxxxxx Xxxx
Xxxxxxx, XX 00000
Article 3 - Reports and Conference
3.1 Oral reports and interim written status reports of the progresses of
the PROJECT (including invention disclosure reports, where appropriate) shall be
provided by NTI to BMS at mutually agreed upon intervals. Significant
developments shall be communicated promptly to BMS. A final report summarizing
the results of the PROJECT shall be submitted to BMS within thirty (30) days of
the conclusion of the PROJECT or any early termination thereof, unless said
termination arises due to breach of a material obligation hereunder by BMS.
3.2 BMS representatives will have reasonable opportunities to consult
informally with NTI representatives by telephone and, upon reasonable notice, to
visit NTI's facility during normal business hours to verify and discuss the
progress and results of the PROJECT.
3.3 From time to time upon reasonable prior notice and at reasonable times
during regular business hours, NTI agrees to permit BMS Quality Assurance and
Drug Regulatory Affairs personnel to inspect NTI's facility and review NTI's
operating procedures and systems to assure that all requirements for GMP
manufacture of GMS and GD2 materials have been satisfied.
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Article 4 - Publicity
4.1 No party hereunder will use the name of the other party in any
promotion or advertising without the prior written approval of an authorized
representative of the other party. If required by law, a party hereunder may
acknowledge the existence of this Agreement and/or the general nature of the
investigations conducted hereunder, provided that prior notice of any such
acknowledgment shall have been given to the other party.
Article 5 - Publications
5.1 NTI may not publish the results of the PROJECT or any portion thereof
without the prior written permission of BMS.
Article 6 - Independent Contractor
6.1 For purposes of this Agreement and in the performance of all services
hereunder, the relationship of the parties hereto shall be one of independent
contractors and not as agents, partners, or employees of one another.
Article 7 - Term and Termination
7.1 This Agreement shall become effective upon the date first hereinabove
written and shall continue in effect until the conclusion of the PROJECT, unless
this Agreement is sooner terminated (i) by mutual written agreement, (ii) by the
nonbreaching party, for breach of a material obligation hereunder by the other
party (which breach is not cured within sixty (60) days following written notice
of such breach) delivered by the nonbreaching party, (iii) by BMS without cause,
upon ninety (90) days written notice to NTI.
7.2 Termination of this Agreement by either party for any reason shall not
affect the rights and obligations of the parties accrued prior to the effective
date of termination of this Agreement. No termination of this Agreement, however
effectuated, shall affect or release the parties hereto from their rights and
obligations under Articles 8, 9 and 10 or under any other provision herein
which, by its intent or meaning, is intended to survive such termination.
Notwithstanding the foregoing, in the event of termination by NTI for reason of
a breach of a material obligation of this Agreement by BMS, the rights and
licenses granted to BMS by NTI under Article 9 of this Agreement shall terminate
and revert to NTI.
7.3 NTI shall be free to manufacture GM2 and GD2 for any purpose outside
the Field upon conclusion of the PROJECT, or upon any early termination pursuant
to the terms of Article 7.
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Article 8 - Confidential Information
8.1 In furtherance of completion of the PROJECT, either party hereunder may
elect to disclose to the other party information which the disclosing party
considers confidential or proprietary ("Confidential Information"). Such
Confidential Information shall be reduced to writing and clearly indicated as
being confidential at the time of disclosure (or, in the case of verbal
information reduced to writing and so marked within a reasonable time
thereafter). Without the prior written consent of the disclosing party, each
party agrees to hold in confidence all of such Confidential Information
disclosed to it hereunder, and will not use any Confidential Information for any
purpose except furtherance of the PROJECT. Each party agrees to take reasonable,
necessary and prudent precautions to protect and to obligate its employees,
contractors and other researchers to protect all Confidential Information
disclosed by the other party to it pursuant to this Agreement. These obligations
shall apply equally to copies and to extracts made of the other party's
Confidential Information. This obligation of confidentiality shall not, however,
apply to information which:
(i) Was known to the receiving party prior to the time of disclosure,
as can be demonstrated by competent written evidence;
(ii) Was part of the public domain prior to the time of disclosure;
(iii) Becomes part of the public domain after the time of disclosure
other than through the act or omission of the receiving party in breach of
this Agreement.
(iv) Becomes known to the receiving party without restriction from a
third party not under an obligation of confidentiality, direct or indirect,
to the disclosing party not to disclose such information to others, as can
be demonstrated by competent proof; or
(v) Is independently developed by the receiving party without regard
to the information disclosed to it by the other party hereunder, as can be
demonstrated by competent proof.
Confidentiality Information may be disclosed as required by applicable law,
provided that the party required to disclose same gives notice to the party from
whom it received the information, and seeks confidential treatment of such
disclosure to the maximum extent permitted by applicable law. Nothing in this
Article 8 is intended or shall be construed as creating or implying any right or
license under any patent rights or other intellectual property rights owned or
controlled by either party by virtue of such party's disclosure of Confidential
Information.
8.2 The parties further agree that all technical information and data
produced in the course of completing the PROJECT shall be deemed
Confidential Information and shall not be
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disclosed by either party to any third party without the prior written consent
of the other party hereunder.
8.3 The obligations of confidentiality set forth in this Article 9 shall be
effective for the duration of this Agreement and for a period of five (5) years
following any termination thereof.
Article 9 - Intellectual Property
9.1 BMS acknowledges that NTI currently holds issued United States Patent
No. 5,180, 674 as well as international equivalents thereof which claim
processes for enzyme synthesis, including a number of process steps which may be
required to synthesize GM2 and GD2 gangliosides from ceramide glucose starting
materials ("NTI Patent Rights").
9.2 BMS and NTI agree that NTI shall own any new technology developed by
NTI in the course of completing the PROJECT ("NTI PROJECT Technology"),
including that technology embodied in a patent application in preparation
relating to the synthesis of GM2 and GD2 from plant ceramide starting material.
9.3 NTI hereby grants BMS an exclusive, worldwide, fully paid-up,
royalty-free license to use NTI Patent Rights for the sole purpose of preparing
GM2 and GD2 gangliosides for any oncologic vaccine or related product for the
term of this Agreement and any extension or continuation thereof.
Article 10 - Indemnification
10.1 BMS agrees to indemnify and hold NTI harmless from any loss, damage or
claim (including, without limitation, attorneys fees) arising from BMS' use of
the GM2 and GD2 materials supplied by NTI hereunder for any purpose, including
clinical studies involving human subjects, except to the extent such claims
primarily arise from the negligence or willful misconduct of NTI in the
preparation of such materials.
Article 11 - Miscellaneous
11.1 This Agreement, together with all Exhibits annexed hereto, constitutes
the entire understanding between BMS and NTI with respect to the PROJECT hereof,
and supersedes and replaces all prior agreements, understandings and writings
between these parties as to said subject matter. Any inconsistency or conflict
between the terms of this Agreement and any Exhibit shall be resolved in favor
of the text of this Agreement.
11.2 Legal notices hereunder shall be deemed made if given by registered or
certified mail, postage prepaid or by any other methods capable of providing
reasonable proof of receipt
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thereof, and addressed to the party to receive such notice at the address first
set forth above or at such other address as may hereafter be designated by a
party in writing.
11.3 This Agreement may be amended or supplemented only by a written
instrument executed by all parties. No provision of this Agreement may be waived
by any act, omission or knowledge of a party or its agents or employees, but
only by a writing expressly waiving such provision and signed by the waiving
party. The failure of a party at any time or times to require performance of any
provision hereof shall in no manner affect its rights at a later time to enforce
the same. No waiver by a party of any condition, remedy or term or any other
condition, remedy or term of any successive occasion.
11.4 No obligations or rights under this Agreement may be assigned or
delegated by NTI without the prior written consent of BMS.
11.5 This Agreement shall be construed, interpreted and governed by the
laws of the State of New Jersey. Captions and paragraph headings are for
convenience only and shall not form an interpretative part of this Agreement.
This Agreement shall not be strictly construed against either party hereto.
11.6 Each party hereby assumes any and all risks of personal injury and
property damage attributable to the acts or omissions of that party and its
trustees, directors, officers, employees, contractors, representatives,
students, post-docs, faculty, and agents in the course of completing the
PROJECT.
11.7 NTI hereby certifies to BMS that NTI will not use the services of any
person debarred under the Generic Drug Enforcement Act of 1992, as amended, in
any capacity in connection with any provided to BMS. NTI shall promptly notify
BMS of any change in the truth of this certification.
IN WITNESS WHEREOF, the parties through their duly authorized
representatives have executed this Agreement in multiple counterparts as of the
date and year first above written.
XXXXXXX-XXXXX SQUIBB NEOSE TECHNOLOGIES, INC.
PHARMACEUTICAL RESEARCH
INSTITUTE
By: /s/ Xxxxxxxxxxx X. Xxxxxxxxx By: /s/ P. Xxxxxxxx Xxxx
-------------------------------------- -----------------------------
Xxxxxxxxxxx X. Xxxxxxxxx, Ph.D. Title: Presdient and CFO
Vice President
Process Research & Development
Date: 6/11/98 Date: 6/11/98
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Tax I.D. No. 00-000-0000
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APPENDIX A
PROJECT SCOPE - GANGLIOSIDE SUPPLY
FROM NEOSE TECHNOLOGIES
Project Goal
NTI shall produce and supply to BMS (1) [*] of xxxxxxxxxxx XX0,
manufactured under GMP conditions from plant derived ceramide within seven (7)
months of the Effective Date of the Agreement and (2) [*], manufactured under
GMP conditions from plant derived ceramide within twelve (12) months of the
Effective Date of the Agreement. The manufacturing process will be designed to
[*]. The [*] of each ganglioside material will be made in three (3) batches of
[*] each.
Project Assumptions
1. Project start date will be the Effective Date of the Research
and Development Agreement.
2. GM2 and GD2 will be developed from a [*] starting material.
3. Milligram quantities [*] of non-GMP GM2 material will be
available within thirteen (13) weeks of project start date.
4. NTI will deliver [*] batch of cGMP GM2 material within
fourteen (14) weeks of delivering a [*] sample of GM2 to BMS.
Upon approval of BMS, NTI will manufacture and deliver two (2)
additional [*] batches of cGMP GM2 to BMS on a biweekly basis.
At NTI's discretion, NTI may complete an intermediate scale of
GM2 batch prior to the first [*] delivery, provided that there
is no impact on the Project Schedule as described in this
Appendix.
5. Milligram quantities [*] of non-GMP GD2 material will be
available within thirty-six (36) weeks of project start date.
6. NTI will deliver [*] batch of cGMP GD2 material within
fourteen (14) weeks of delivering a [*] sample of GD2 to BMS.
Upon approval of BMS, NTI will manufacture and delivery two
(2) additional [*] batches of
--------------------
[*] We are seeking confidential treatment of these terms, which have been
omitted. The confidential portion has been filed separately with the Securities
and Exchange Commission.
1
cGMP GD2 to BMS on a biweekly basis. At NTI's discretion, NTI may
complete an intermediate scale GD2 batch prior to the first [*]
delivery, provided that there is no impact on the Project Schedule as
described in this Appendix. At BMS' discretion, BMS may reduce the
specified batch size (stated herein as [*]) prior to start of
manufacture, as clinical needs are established.
The research and development program required to meet the project
assumptions stated above will be funded according to the following payment
structure:
1. Project Start (Project Initiation Fee) $[*]
2. Delivery of mg quantities of non-GMP GM2 $[*]
3. Delivery of full [*] of cGMP GM2 $[*]
4. Delivery of mg quantities of non-GMP GD2 $[*]
5. Delivery of full [*] of cGMP GD2 $[*]
The total cost for this Research and Development Agreement will be $[*] and
include all costs associated with the preparation of documentation required for
cGMP practices as well as the actual manufacturing costs of non-GMP and GMP
deliveries of both gangliosides.
In the event that BMS requests the [*] deliveries of either ganglioside be
manufactured without strict cGMP controls (as may be occasioned by the granting
of "Starting Material" status by the FDA), the royalty payment will be modified
as follows:
Item No. 3 - Delivery of full [*] of cGMPGM2: $[*]
Item No. 5 - Delivery of full [*] of cGMP GD2 $[*]
NTI will commit to supplying all quantities of ganglioside required by BMS
for product development purpose (process development and validation, product
stability, clinical trials, etc.) For requirements in excess of the [*] batches
of each GM2 and GD2, the price per gram shall be $[*] for cGMP material and $[*]
for non-GMP material.
Development Terms
1. NTI will reserve all quantities of gangliosides prepared
during the process development trials (regardless of quality)
for transfer to BMS, except that NTI may retain such
quantities of GM2 and GD2 as are necessary for the maintenance
of standards, analytical methods and quality control. Excess
quantities of ganglioside transferred to BMS hereunder will be
used to assist BMS in refining analytical methods and
developing specifications for the gangliosides.
-----------------
[*] We are seeking confidential treatment of these terms, which have been
omitted. The confidential portion has been filed separately with the Securities
and Exchange Commission.
2
2. BMS and NTI will develop complete documentation of the
manufacturing process for the preparation of GM2 and GD2. In
the event that NTI is incapable of meeting or unwilling to
meet BMS' production requirements for either GM2 or GD2, BMS
and NTI will work together to transfer NTI technology to a
mutually agreed upon third party or to BMS' internal
manufacturing network.
3. In the event NTI is unable to offer acceptable quality
ganglioside material derived from plant ceramide in the time
agreed to in the Research and Development Agreement, NTI will,
upon request from BMS, revert to the production of
gangliosides from [*]. Monies paid to support the [*] route
will be transferred directly the [*] process development
effort.
----------------------
[*] We are seeking confidential treatment of these terms, which have been
omitted. The confidential portion has been filed separately with the Securities
and Exchange Commission.
3
