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EXHIBIT 10(n)
EXCLUSIVE LICENSE AND DISTRIBUTION AGREEMENT
between
CEL-SCI CORPORATION
a corporation incorporated under the laws of the State of
Colorado, of 8229 Boone Boulevard, Suite 802,
Vienna, VA 22182, USA
("Supplier")
and
TEVA PHARMACEUTICAL INDUSTRIES LTD
a limited liability company incorporated under the laws of
Israel, of 5 Basel Street, Petah Tiqva
49131, Israel
("Teva")
WHEREAS Supplier is developing the Product defined below for approval in the
placecountry-regionU.S. and other countries in the world; and
WHEREAS Teva has the facilities, personnel and technical expertise and
capability to assist in the clinical trials done with the Product, obtain
regulatory approval for the Product, and market and distribute the Product in
the Territory and desires to undertake such activities in accordance with the
terms and conditions of this Agreement; and
WHEREAS Supplier has the know-how and facilities to manufacture or procure the
manufacture the Product and is prepared to supply the Product and to grant to
Teva the right and license to exclusively distribute the Product in the
Territory subject to the terms and conditions set out below.
NOW THEREFORE THE PARTIES AGREE AS FOLLOWS:
1. INTERPRETATION AND DEFINITIONS
1.1. The preamble to this Agreement forms an integral part hereof.
1.2. Clause headings in this Agreement are intended solely for convenience of
reference and shall be given no effect in the interpretation of this
Agreement.
1.3. All appendices to this Agreement, whether attached at the time of signature
hereof or signed by the parties at any time thereafter, shall be construed
as an integral part of this Agreement.
1.4. In this Agreement, the following expressions shall bear the meanings
assigned to them below and cognate expressions shall bear corresponding
meanings.
1.4.1. "Affiliate" - with respect to either party, means any person,
corporation, company, partnership or other entity controlling,
controlled by or under common control with such party. For such
* Confidential treatment requested. Confidential portion has been omitted and
filed separately with the Securities and Exchange Commission.
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purpose the term "control" means the holding of 50% or more of the
common voting stock or ordinary shares in, or the right to
appoint 50% or more of the directors of, the said corporation,
company, partnership or entity.
1.4.2. "the Territory" - collectively placecountry-regionIsrael (including
the adjacent territories under its administration and/or the
administration of the Palestinian Authority) and
placecountry-regionTurkey.
1.4.3. "a Country" - individually, any one of the countries forming part of
the Territory.
1.4.4. "the Effective Date" - the date of signature of this Agreement.
1.4.5. "the Regulatory Approval" - the approval by the respective
regulatory authorities, in the Territory, of the marketing,
distribution and sale of the Product, in the Territory.
1.4.6. "the Approval Dates" - with regard to a particular Country, the date
on which the regulatory authorities and all other relevant authorities
in such Country, grant the Regulatory Approvals and all other relevant
authorizations necessary for the importation, promotion, marketing,
distribution and sale of the Product in such Country.
1.4.7. "the Launch Date" - with regard to a particular Country, the date on
which a Product is first commercially sold in such Country.
1.4.8. "the Product" - the finished form pharmaceutical compositions
manufactured in accordance with the Specifications (as defined below)
and described in Appendix A, including any dosage forms and strengths,
drug delivery forms, modifications and/or improvements of such
compositions. Supplier will update Appendix A from time to time during
the term of this Agreement to reflect the addition of any dosage forms
and strengths, drug delivery forms, modifications and/or improvements
of the composition described on Exhibit A as of the date hereof.
1.4.9. "the Substance" - the bulk active ingredient used in the manufacture
of the Product.
1.4.10. "the Field" - the treatment of head and neck cancer in humans.
1.4.11. "Formulation" - the manufacture of the Product utilising, inter
alia, the Substance, on the basis of the Formulation Technology.
1.4.12. "the Formulation Technology" - all of the technological know-how
and expertise required for the Formulation of the Product including
without limitation analytical methodology and controls, the precise
composition of the Formulation of the Product, the working procedure
for the Formulation and all documentation with regard to the
foregoing, as specified in the relevant dossier.
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1.4.13. "the Specifications" - the specifications identified in Appendix B
with regard to the Product, as may be amended from time to time by
Supplier (with written notice to Teva), prior to regulatory approval
in a Country in Supplier's discretion, and following regulatory
approval in a Country, with the agreement of Teva and Supplier which
shall not be unreasonably withheld or delayed. For clarity, any
changes to the Specifications under this Agreement shall not modify
Teva's obligations under the Clinical Trial Agreement.
1.4.14. "Quarter" means a complete period consisting of the months of
January to March, April to June, July to September, and October to
December, all inclusive.
1.4.15. "Information" - any and all information acquired in the course of
the negotiation and performance of this Agreement disclosed by either
party herein, or which either party acquires relating to the business,
finance or trade secrets of the other party.
1.4.16. "GMP" - standards of current Good Manufacturing Practice as laid
down and as accepted from time to time by the United States Food and
Drug Administration and the International Conference on Harmonisation
of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH).
1.4.17. "Material Events" events (not within the reasonable control of
either party) which have a significant direct adverse or significant
beneficial impact on the position and/or marketability and/or sales of
the Product in the Territory during a given period or on the parties'
economic interests under this Agreement, such as, for example - but
without limitation:
1.4.17.1. the entry into the market of significant new competing
products or significant therapeutic concepts including
significant generic competition, and/or the cessation of
significant competing products in the market in any Country;
1.4.17.2. the loss of or increase in a significant reimbursive
allowance by a medical insurance fund;
1.4.17.3. significant changes in the social security system in any
Country which affect the upper limit on medical practitioners'
budgets for patient's medication;
1.4.17.4. a change in the specifications of any Substance and/or
Product, resulting in an adverse impact on Supplier's cost of
Formulation of the Product;
1.4.17.5. a significant increase in Supplier's cost of Formulation of
the Product.
1.4.18. "the Material Event Procedure" - the procedure outlined, to be
followed on the occurrence of a Material Event.
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1.4.19. "Net Sales" - the total amount actually received by Teva or its
Affiliates from the arms length sale of the Product, provided that as
to sales other than at arms length, the term "Net Sales" shall mean
the total amount that would have been due in an arms length sale,
according to the then current conditions for such sale or - in the
absence of such current conditions - according to reasonable
conditions for such sale, in all cases after deduction of:
1.4.19.1. sales taxes (including value added taxes) to the extent
applicable to sales of the Product and not collected separately
from the counter-party to such sales; and
1.4.19.2. credits or allowances, if any, actually granted, and
approved by Supplier, on account of price adjustments, recalls,
rejections or return of the Product previously sold; and
1.4.19.3. all shipment, storage, transportation and other direct
administrative expenses required for the distribution of the
Product.
and provided further that as to sales by Teva to its Affiliates, or
between Affiliates of Teva, the terms "Net Sales" shall mean the
higher of (i) "Net Sales" as defined above, with respect to sales
other than at arms length; and (ii) the total amount actually
received by Teva or the Affiliate, on resale to an independent third
party purchaser after the deductions specified in Clauses 1.4.19.1,
1.4.19.2 and 1.4.19.3 above, to the extent applicable.
1.4.20. "Manufacturing Cost" means the actual costs of manufacturing and
supplying Product to Teva under this Agreement, which shall be the sum
of the following costs, all of which shall be calculated on a per-unit
basis and in accordance with placecountry-regionU.S. generally
accepted accounting principles consistently applied:
1.4.20.1. The amounts paid by Supplier to a third party for (i)
providing raw materials and packaging materials for producing the
Product, (ii) storing, transporting, and insuring the Product
(but excluding any transportation or insurance costs for which
Teva is responsible), (iii) release testing of the Product, and
(iv) taxes (other than income taxes) and customs duty charges
imposed by governmental authorities with respect to the
manufacture or supply of the Product, in each case to the extent
paid by Supplier and not reimbursed or refunded or credited to
Supplier, and net of any discounts or other benefits received by
Supplier from third party manufacturers that provide goods or
services to Supplier with respect to Product; and
1.4.20.2. The direct costs and charges incurred by Supplier in
connection with the manufacture, filling, finishing, testing,
labeling, packaging, storage, release, shipping and
transportation of the Product (but excluding any shipping,
transportation or insurance costs for which Teva is responsible).
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Notwithstanding the foregoing, no cost, charge, or expense will be
included in more than one of Clauses 1.4.20.1 and 1.4.20.2.
1.4.21. "Supplier House Mark" means any trademark, trade name, domain name,
or other name or mark used or registered by Supplier or its Affiliate
to identify itself at any time during the term of this Agreement.
1.4.22. "Product Trademark" means any trademark, trade dress (including
packaging design), logo, slogan, domain name and design, whether or
not registered in a country or territory, selected in writing and
owned by Supplier and used to identify or promote the Product.
2. APPOINTMENT OF DISTRIBUTOR, DURATION
2.1. Subject to the terms of this Agreement, Supplier hereby grants Teva the
sole and exclusive right and license to market, distribute and sell the
Product for the Field in the Territory and in accordance with the terms of
this Agreement, and Teva accepts such right and licence. Teva may not
sublicense or delegate such right except in accordance with the terms of
Clause 24 below.
2.2. This Agreement shall commence on the date hereof and unless terminated
earlier in accordance with Clause 11 below, shall continue in each Country
comprising the Territory, on a Product-by-Product basis, for an initial
fixed term of ten (10) years from the Launch Date of each Product in the
Country respectively. Without derogating from Clause 11, such initial term
shall be renewed automatically, for additional successive terms of two (2)
years each, unless either party provides the other with written notice, by
not later than six (6) months before the scheduled commencement of any
such renewal term, not to renew this Agreement in the relevant Country,
either as a whole or with regard to any particular form or composition of
the Products.
2.3. Following the Launch Date of a Product, Teva shall be entitled at any time
in its reasonable discretion to cease selling such Product in the
Territory or in any one or more Countries comprising the Territory, for
reasons of (i) medical safety, (ii) on legal or regulatory grounds or
(iii) in the event that the Product, in any dosage form thereof, cannot be
sold at a price which will facilitate Teva being able to show a profit
(section 2.3(iii) shall be referred to as "Commercial Reasons"); provided
that, Teva has notified Supplier in writing six (6) months in advance of
its intention to cease sales of the Product in any specific Country for
Commercial Reasons or has notified Supplier in writing as soon as
practical for all other reasons. Promptly following such cessation, the
parties shall meet and in good faith discuss the reasons for such
cessation and the modifications, if any, to this Agreement to address the
cause of such cessation. If such cessation due to Commercial Reasons
continues for at least six (6) months in a Country, then Supplier shall
have the right to terminate this Agreement solely with respect to the
affected Country upon sixty (60) days' prior written notice to Teva.
3. REGISTRATION
3.1. Teva shall file applications for, obtain, and maintain the Regulatory
Approvals with regard to each Product by the regulatory authorities in the
Territory; provided, that to the extent permitted by applicable laws in
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the Territory, Supplier will provide any chemistry, manufacturing and
control information and clinical results necessary to obtain such
Regulatory Approvals directly to the relevant authorities. Such
applications shall be filed by Teva as soon as possible after the US/EU
Launch Date (as defined below), and by not later than six (6) months after
compliance by Supplier with Clauses 3.2 and 3.3 below; provided, that if
Teva can show that the preparation of registration dossiers of an
acceptable standard, on the basis of the documentation and information to
be received by it pursuant to this Agreement will require more than six
(6) months of preparation, then such period will be extended for such time
as reasonably necessary to prepare such dossiers. All Regulatory Approvals
shall be held by Teva in its name or the name of its nominee, and Teva
shall be the owner thereof, subject to the terms and conditions of this
Agreement. Teva shall fund the cost of procurement of the Regulatory
Approvals. Teva agrees to comply in all respects with all applicable laws,
legislation and/or regulations in the Territory in force from time to
time. "US/EU Launch Date" means, with respect to a Product, the earlier
of: (i) the date on which Supplier has first sold such Product in the
placecountry-regionU.S.A. following the receipt of marketing approval of
the regulatory authorities in the U.S.A and, (ii) the date on which
Supplier has first sold such Product in the European Union following the
receipt of marketing approval of the regulatory authorities in the
European Union (either through the centralized EMEA approval procedure or
through the national approval procedures of any of the following
countries: placecountry-regionFrance, placecountry-regionGermany,
placecountry-regionItaly, placecountry-regionSpain, or the
placecountry-regionUnited Kingdom).
3.2. Within thirty (30) days of the US/EU Launch Date for a Product, Supplier
will provide Teva with such documentation as may be required by Teva for
the purposes described in Clause 3.1 above, including without limitation
the product registration dossier/s with regard to such Product.
3.3. Within thirty (30) days of the US/EU Launch Date for a Product, Supplier
shall make available to Teva, and Teva shall have the right to utilise for
the purposes described in Clause 3.1 above, within the Territory only, all
clinical data in Supplier's possession or control with regard to such
Product, and any regulatory submissions for the Product; provided, that
Supplier shall not be obligated to provide such data or submissions to
Teva if such action would violate any obligations of confidentiality and
non-use that may be imposed on Supplier by its third party collaborators
with respect to data or submissions generated by such third parties.
Supplier shall use its reasonable efforts to cause such third party
collaborators to agree to the open exchange of such data and submissions
among Supplier and its various collaborators throughout the world for the
purposes of obtaining Regulatory Approval of the Product. For clarity,
clinical data and regulatory submissions generated by Supplier itself
shall be made available to Teva pursuant to this Clause 3.3 in any event.
4. TEVA'S UNDERTAKINGS
Teva undertakes and agrees with effect from the Effective Date and at all
subsequent times during the term of this Agreement:
4.1. to use all reasonable endeavours to seek regulatory approval for, market
and sell the Product in the Territory at its own cost and expense and
subject to the terms and conditions of this Agreement, subject to the
conditions set out in Clause 10, except where expressly agreed otherwise in
writing;
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4.2. to maintain adequate facilities at all times, including competent and
experienced personnel and officers, and where required, storage and
distribution facilities, to enable Teva to perform its obligations under
this Agreement, including the management of all customer relationships,
complaints, and returns;
4.3. to purchase (and cause its Affiliates to purchase) the Product only from
Supplier for the Territory;
4.4. to inform Supplier from time to time of any matter in the Territory likely
to affect, significantly, the Formulation and/or promotion, marketing and
sale of the Product, including any alleged infringement of third party
intellectual property rights;
4.5. to use reasonable endeavors to prevent any sale, supply and/or export of
the Product to customers outside the Territory by Teva or its customers;
4.6. to inform Supplier of any complaints or information relating to the use or
quality of the Substance or the Product or of any matter that may give
rise to a product recall (as described in greater detail in the
Pharmacovigilance Agreement referenced in Clause 13), but subject to the
requirements of law or the regulatory authorities in the Territory, not to
take any action with regard thereto without obtaining Supplier's prior
written consent, such consent to be provided promptly and not unreasonably
withheld by Supplier; and
4.7. not to make any promise or guarantee or representation whatsoever with
reference to the Product beyond those contained in the material supplied
by, or approved in writing by, Supplier without Supplier's prior written
consent.
5. SUPPLIER'S UNDERTAKINGS
Supplier undertakes and agrees with Teva with effect from the Effective Date and
at all subsequent times during the term of this Agreement:
5.1. to maintain the timely supply of the Product (as may be decided by the
parties during the terms of this Agreement) for sale by Teva according to
the forecasts provided by Teva and agreed by Supplier;
5.2. to supply Teva with the Product in finished form, labeled and packed in
accordance with the Specifications, GMP, the requirements of the
regulatory authorities of the placecountry-regionU.S.A. and European
Union, as applicable, and the terms and conditions of this Agreement. In
addition, the Product's labeling for the Territory shall be prepared in
accordance with Teva's written requirements for compliance with Teva's
requirements (subject to Supplier's consent which shall not be
unreasonably withheld or delayed) and the regulatory requirements in the
Territory;
5.3. to use reasonable endeavors to manufacture Product in accordance with any
special regulatory requirements for the Territory as may be identified by
Teva in writing from time to time;
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5.4. to use reasonable endeavors to prevent parallel import and to prevent any
sale, supply and/or import of the Product to the Territory by third
parties;
5.5. to provide Teva with any and all reasonable assistance required for the
marketing and distribution of the Product (in each case, to the extent
available to the Supplier), including without limitation, information,
publications, marketing materials (as described in greater detail in
Clause 17.2 below) and new developments regarding the Product, commercial
activities and any other information which might be relevant for the
marketing and distribution of the Product; and
5.6. to bear all costs associated with product recalls, other than recalls
initiated as a result of actions directly attributable to Teva's gross
negligence or willful misconduct; and
5.7. to inform Teva as soon as is practical of any changes in Supplier's
organization or method of doing business which might affect the carrying
out by Supplier of its duties hereunder.
6. FORECASTS AND ORDERS; AUDITS
6.1. As soon as practicable after execution of this Agreement and in any event
by not later than the date one hundred and twenty (120) days prior to the
anticipated Approval Date for either Country in the Territory, Teva shall
submit to Supplier a forecast of its requirements of the Product for the
first four Quarters immediately following the then anticipated Launch
Date. At least one hundred and twenty (120) days before the commencement
of each subsequent Quarter, Teva shall submit to Supplier an updated
forecast of its requirements of the Product for the next four Quarters.
Such forecasts shall be Teva's best estimate but shall not be binding,
save as set out in Clause 6.2. Supplier may review and accept or modify
any such forecasts submitted by Teva within ten (10) days of such
submission and will inform Teva if the forecasted amounts of Product are
likely to exceed Supplier's available capacity and inventory for the
forecasted period. After the initial forecast, for each subsequent
forecast the second quarter in such forecast (i.e., the quarter which is
now binding but was in the most recent prior forecast considered to be
non-binding) may not vary (either up or down) by more than fifty percent
(50%) from the amounts forecasted to be ordered for such period in the
most recent prior forecast submitted by Teva, except with the consent of
Supplier.
6.2. The forecast for the first Quarter referred to in Clause 6.1 and the first
Quarter of each updated estimate submitted pursuant to Clause 6.1 above
shall constitute a binding order by Teva. Teva may order amounts of
Product in excess of the amounts forecast for such Quarter, and Supplier
shall use commercially reasonable efforts to supply any such additional
amounts ordered; provided, that Supplier shall be under no obligation to
accept purchase orders for amounts exceeding one hundred twenty percent
(120%) of the amount forecast for such Quarter. The quantities indicated
for the remaining months of each rolling forecast will be treated as a
forecast only and will not create any obligations for either Party.
6.3. All Product ordered under this Agreement shall be pursuant to written
purchase orders, each of which shall specify the quantity of clinical
and/or commercial Product ordered and the requested delivery date. Teva
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shall submit each such purchase order to Supplier no later than one
hundred and twenty (120) days prior to the delivery date indicated in such
purchase order. Any purchase orders for Product submitted by Teva shall
reference this Agreement and shall be governed exclusively by the terms
contained herein, and shall be consistent with the terms of this
Agreement, including this Article 6. Any term or condition in any order,
confirmation or other document furnished by Teva or Supplier that is in
any way inconsistent with the terms and conditions of this Agreement is
hereby expressly rejected. Orders placed by Teva shall be subject to
acceptance by Supplier. Supplier will provide Teva with written notice of
acceptance of all orders, within ten (10) business days of the placement
thereof (for those binding forecasts accepted as described in Clause 6.1
above), save in the case of any excess orders (as described in Clause 6.2
above) or Supplier being unable, for objective good cause which is not due
to the Supplier's act and/or omission (and not due to a lack of capacity),
to fulfill any order in whole or in part.
6.4. Risk and title to the Product shall pass to Teva when such Product is
tendered to the carrier at the designated point for shipment by air
transport from the placecountry-regionUnited States of America (FCA,
Incoterms 2000). In addition, Supplier shall be in charge of arranging for
the shipment and insurance (and paying for such amounts) of the Products
to Teva's designated customs point in Israel. Teva shall reimburse
Supplier for such amounts promptly upon submission of an invoice for such
payments and shall be entitled to deduct such amounts paid from the Net
Sales.
6.5. In the event that Supplier is unable to supply all orders on time,
Supplier agrees to provide Teva with order status reports at least once a
week in a format to be agreed. Such reports shall document the
manufacturing capacity of Supplier at the date of each respective report,
the stages which Supplier is taking to return to timely deliveries, and
the anticipated date of delivery of all outstanding orders, as well as any
other information which Teva may reasonably require at such time.
6.6. Upon written request to Supplier, Teva shall have the right no more than
once per calendar year to have representatives visit the manufacturing
facilities of Supplier during normal business hours to review
manufacturing operations, to assess its compliance with GMP and quality
control procedures, and to discuss any related issues with Supplier's
manufacturing and management personnel. During the term of this Agreement,
Supplier shall permit any regulatory authority from the
placecountry-regionU.S.A., European Union or Territory which wishes to
audit such facilities to do so, in order to ensure compliance by Supplier
with the quality standards referred to above.
6.7. If Supplier's output of Product is reduced or if Supplier is otherwise
unable to satisfy its outstanding orders of Product (e.g., due to
unanticipated demand), Supplier shall satisfy any of Teva's outstanding
binding purchase orders by allocating its available supply among Teva,
Supplier's other customers, and Supplier's own requirements for sale in
territories retained by Supplier in a fair and equitable manner as
reasonably determined by Supplier, and in accordance with each such
recipient's pro rata share of Product sales during the previous four (4)
Quarters. The allocation mechanism described in this Clause 6.7 will not
derogate from Teva's rights or remedies under this Agreement with respect
to ordered quantities of Product that are not delivered by Supplier in
accordance with the terms of this Agreement.
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7. PRICE AND TERMS OF PAYMENT
7.1. Participation in clinical trials: Teva shall take upon itself, at its
cost, the performance of certain activities related to the conduct of a
clinical trial in placecountry-regionIsrael, as part of a global Phase 3
trial for the Product, as described in further detail in the clinical
trial agreement attached to this Agreement as Appendix D (the "Clinical
Trial Agreement"). For the avoidance of doubt, any obligation of a party
under the Clinical Trial Agreement shall be treated as an obligation under
this Agreement.
7.2. Price: The amounts to be paid by Teva to Supplier in connection with the
supply of Product shall be as follows:
(a) for supplies of Product to be used for the conduct of activities
under the Clinical Trial Agreement, a service charge for providing the
Product equal to **** ******* *** ***** ***** US Dollars per vial of
Product (as described in the Specifications); and
(b) for all other supplies of Product, the greater of: (i) * percent
of the Net Sales of such Product, and (ii) * percent (*%) of Supplier's
Manufacturing Cost for such quantity of Product.
7.3. With every delivery of the Product to Teva, Supplier shall send Teva an
invoice. For commercial supplies of Product, the initial transfer price
for each unit of Product shall be based upon the average Net Sales per
unit as described in the latest Sales Certificate (defined below). All
payments shall be made within thirty (30) days from the last day of the
month in which the invoice was issued, in a manner of a bank transfer to a
bank account number, provided by Supplier to Teva sufficient time in
advance of such bank transfer.
7.4. Within thirty (30) days of the end of each Quarter, Teva shall prepare and
deliver to Supplier a certificate ("the Sales Certificate") setting out
details of the Net Sales of the Product by Teva during the relevant
Quarter, including the gross sales price and any deductions described in
the definition of Net Sales. Notwithstanding the foregoing, Teva shall
prepare and deliver the first placeCitySales Certificate together with its
first order of Products for non-clinical use. All Sales Certificates for
periods prior to the Launch Date will include Teva's reasonable non
binding estimate of the anticipated sales price and relevant deductions.
7.5. At the end of each calendar year, Teva will prepare a summary of the
previous year's Net Sales and will calculate the payments already paid by
Teva and a true-up payment will be made by the applicable party in order
to reconcile the amounts paid with the purchase prices described in Clause
7.2.
7.6. To the extent that sales are effected by Teva, other than in United States
Dollars, Teva shall convert the sum of such sales into US Dollars in
accordance with the selling rate for such currency quoted in the Wall
Street Journal last published on the business day on which Teva remits
payment to Supplier.
7.7. Teva shall keep full and true books of account and other records in
accordance with generally accepted accounting practice in
Israel so that details of sales of the Product, and
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Teva's payment obligations in respect thereof, may be properly
ascertained. Teva shall preserve such books and records for three (3)
years after the calendar year to which they pertain. Such books and
records shall be open to inspection by an independent certified public
accountant selected by Supplier, and subject to confidentiality
obligations as strict as in this Agreement, at Supplier's expense, during
normal business hours upon ten (10) business days' prior written notice,
for the purpose of verifying the accuracy of the reports and computations
rendered by Teva. In the event Teva underpaid the amounts due to Supplier
with respect to the audited period by more than five percent (5%), Teva
shall pay the reasonable cost of such examination, together with the
deficiency not previously paid, within thirty (30) days of the last day of
the month of the date of receipt of notice from Supplier.
7.8. Other than V.A.T. and comparable taxes, all payments by Teva are inclusive
of all taxes and/or duties, of whatsoever nature, which are now or may
hereafter be imposed with regard to any such payments, including without
limitation withholding taxes.
8. WARRANTY AND INSPECTION
8.1. Supplier warrants that at the time of delivery, the Product shall meet the
Specifications.
8.2. At the time of delivery of each consignment of the Product, Supplier shall
deliver a Certificate of Analysis showing that the relevant Product
conforms to the Specifications.
8.3. Teva may elect to inspect each consignment of the Product within forty
five (45) days of receipt of the Certificate of Analysis from Supplier.
8.4. In the event that the Product is shown by Teva to be not in accordance
with Specifications on receipt, or if there is a shortfall in the number
of the Product contained in the delivered consignment, then Teva shall
notify Supplier to this effect no later than sixty (60) days after receipt
of the Product in question. If no such notice of rejection is received by
Supplier within such sixty (60) day period, Teva shall be deemed to have
accepted such shipment of Product, except with respect to any Latent
Defect, as defined below. Once Teva accepts, or is deemed to have
accepted, a shipment of Product, Teva shall have no recourse against
Supplier under this Clause 8 if the Product is subsequently deemed
unsuitable for use for any reason, except with respect to any Latent
Defect. If Supplier disagrees with Teva's determination that certain
Product does not meet the Specifications, such Product shall be submitted
to a mutually acceptable third party laboratory. Such laboratory shall
determine whether such Product meets the Specifications, and the Parties
agree that such laboratory's determination shall be final and
determinative. The Party against whom the third party laboratory rules
shall bear all costs of the testing. If such laboratory determines or the
Parties agree that such shipment meets the Specifications, then such
shipment shall automatically be deemed to have been accepted by Teva, and
Teva shall pay the purchase price for the quantities of Product initially
rejected by Teva. As used in this Clause 8.4, "Latent Defect" means any
Product defect, including without limitations, non-conformity with the
Specifications that could not have been revealed by Teva's visual
inspection of Product or upon inspection of the corresponding Certificate
of Analysis.
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8.5. In the event that Supplier agrees, or the third party laboratory
determines, that a shipment of Product contains non-conforming goods or a
shortfall, then Supplier shall replace, at its own cost and expense, the
defective quantity, or make up the shortfall as the case may be or, at its
option, allow Teva credit for the defective quantity or shortfall,
whichever is appropriate.
8.6. Supplier hereby represents and warrants that, to its actual knowledge as
of the Effective Date the manufacture, use or sale of the Product in the
Territory as contemplated in this Agreement and Teva's activities in
connection with this Agreement will not constitute an infringement of the
intellectual property rights of any third party. In the event that either
party is made aware of any infringement, as mentioned above, it will
notify the other party of such fact immediately.
8.7. THE EXPRESS WARRANTIES IN THIS CLAUSE 8 ARE IN LIEU OF ALL OTHER
WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, ANY
WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE,
NON-INFRINGEMENT, OR NON-MISAPPROPRIATION OF THIRD PARTY INTELLECTUAL
PROPERTY RIGHTS, AND EACH PARTY HEREBY EXPRESSLY DISCLAIMS ALL OTHER
WARRANTIES WITH RESPECT TO THE PRODUCT.
9. NO REPRESENTATIONS BY TEVA REGARDING THE PRODUCT
Teva shall make no statement, representation or warranty, oral or written,
concerning the Product beyond, inconsistent with or contrary to the Product
labelling, promotional materials or other information or representation made by
Supplier to Teva or any other third party. From time to time, Teva shall provide
Supplier with copies of such promotional materials to enable Supplier to verify
Teva's compliance with the terms of this Clause 9.
10. MATERIAL EVENTS
10.1. In the event that either of the parties is of the opinion that a
Material Event has occurred such party shall be entitled to provide
the other party with written notice ("Material Event Notice") setting
out: 10.1.1. that such Material Event has occurred;
10.1.2. a reasonable description of the nature of such Material Event and
the potential consequences thereof;
10.1.3. proposals as to how to react and possible need for modifications to
the contractual obligations of the parties as a result of such
Material Event.
10.2. As soon as reasonably possible after receipt of a Material Event Notice,
but within not more than thirty (30) days of receipt thereof, the
recipient of the Material Event Notice shall provide the sender of such
notice with its written reaction to the Material Event Notice in which the
said recipient shall set out any counter-proposals it may have to the
proposals of the sender of the Material Event Notice.
12
10.3. Within not more than sixty (60) days of delivery of the Material Event
Notice, the parties shall meet in order to review, jointly, in good faith,
the Material Event and the respective proposals of the parties, as well as
in order to negotiate, in good faith, the possible modification, if any,
of the parties' contractual obligations required by such Material Event.
10.4. Notwithstanding anything to the contrary in this Agreement, if the
Material Event relates to a requirement by a regulatory authority for
additional clinical trials or activities other than those included in
Supplier's regulatory submissions for the Product in the U.S.A. and
European Union, then Teva shall have the option to (i) have the parties
meet in order to review, jointly, in good faith, the Material Event and
the respective proposals of the parties, as well as in order to negotiate,
in good faith, its possible solutions, or (ii) terminate this Agreement
upon sixty (60) days' written notice with respect to the Countries
affected by such Material Event. If the good faith negotiations described
in clause (i) above do not result in a mutually agreeable solution to the
Material Event within one hundred and twenty (120) days after the start of
such negotiations, or such longer term as agreed upon by the parties in
writing, then either party may terminate this Agreement upon thirty (30)
days' written notice with respect to the countries affected by such
Material Event. For clarity, until the parties reach mutual understanding,
neither party will be obligated to perform the additional activities
required by a regulatory authority for approval in the Territory.
11. TERMINATION
11.1. Without prejudice to any other rights to which it may be entitled, either
party may give notice in writing to the other terminating this Agreement
if:
11.1.1. the other party is in breach of any of the material terms hereof
and (if such breach is remediable) fails to remedy such breach within
sixty (60) days of that party being notified of such breach; or
11.1.2. the other party admits or is declared insolvent or voluntary or
involuntary proceedings is instituted by or against it in bankruptcy,
or receivership, or for a winding-up or for the dissolution or
re-organisation of its assets; provided, in each case, that such
proceedings are not dismissed within ninety (90) days.
11.2. Supplier may terminate this Agreement with respect to a particular Country
as described in Clause 2.3 following Teva's cessation of Product sales in
such Country.
11.3. Teva may terminate this Agreement as described in Clause 24 in the event
of certain assignments of this Agreement by Supplier.
12. EFFECTS OF TERMINATION
12.1. Termination or expiration of this Agreement howsoever caused shall be
without prejudice to any other rights or liabilities accrued at the date
of termination or expiration (including without limitation Teva's
obligation to pay to Supplier sums due in respect of firm orders of
Product submitted prior to termination or expiration of this Agreement).
13
12.2. Upon termination or expiration of this Agreement, Teva shall promptly
notify Supplier of the quantities of the Product held by it in its
inventory. Teva shall be permitted to sell and distribute the Product in
its inventory for a period of six (6) months following such termination or
expiration, on the basis that the rights and obligations of the parties
under this Agreement shall continue to apply to such sales of Product.
12.3. Upon termination or expiration of this Agreement, subject to Teva's rights
under Clause 12.2 above, Teva shall transfer to Supplier or its designee,
at Supplier's expense, all materials, documentation, regulatory filings,
marketing approvals, and other items as are reasonably necessary for
Supplier to continue the development and sale of each Product in the
Territory. The assignment to Supplier of any intellectual property
generated during the course of Teva's performance of clinical activities
pursuant to the clinical trial agreement shall be made pursuant to such
agreement.
12.4. The provisions of Clauses 12, 13, 14, 16, 19, and 28 shall survive the
termination or expiration of this Agreement. The Clinical Trial Agreement
shall survive the expiration or termination of this Agreement in
accordance with the terms thereof. For clarity, any termination of the
Clinical Trial Agreement under Section 8.3 of the Clinical Trial Agreement
shall not terminate this Agreement.
13. ADVERSE EFFECTS AND RECALLS
13.1. Each party shall execute the Pharmacovigilance Agreement attached hereto
as Appendix C, which agreement shall take effect upon the recipient of
first regulatory approval of the Product in a Country of the Territory.
14. LIABILITY AND CROSS-INDEMNIFICATIONS
14.1. Supplier shall indemnify and hold Teva, its Affiliates, and the officers,
directors and employees of each of them, harmless from any and all
liability, including liability for death or personal injury and reasonable
attorney's fees, to the extent resulting from a third party claim of
negligence or willful misconduct of Supplier with regard to the Substance
and/or Product and/or Product Trademarks, including without limitation,
the manufacture, packaging, delivery and/or supply of the Product.
14.2. Teva shall indemnify and hold Supplier, its Affiliates, and the officers,
directors and employees of each of them, harmless from any and all
liability, including liability for death or personal injury and reasonable
attorneys fees, to the extent resulting from a third party claim of
negligence or willful misconduct of Teva with regard to the promotion and
marketing of the Product and the sale and distribution of the Product.
14.3. In the event that the negligence of Teva, on the one hand, and Supplier,
on the other hand, contributes to any loss, cost, damages, claim or
14
expense relating to the Substance and/or Product supplied and/or
distributed or sold hereunder, then Teva, on the one hand, and Supplier,
on the other hand, shall be responsible for that portion of the loss,
cost, damages, claim or expense to which its negligence contributed.
14.4. Each party seeking indemnification hereunder (the "Indemnified Party")
will inform the other party (the "Indemnifying Party") in writing
immediately or as soon as possible of any claim which may be brought
against the indemnified party as set out above; provided, the failure to
provide such notice within a reasonable period of time shall not relieve
the Indemnifying Party of any of its obligations hereunder except to the
extent the Indemnifying Party is prejudiced by such failure. The
Indemnified Party shall cooperate with the Indemnifying Party and its
legal representatives, at the Indemnifying Party's expense, in the
investigation, negotiation, compromise, settlement and defense of any
action, claim or other matter covered by this indemnification. The
Indemnifying Party shall be in charge of and control any such
investigation, negotiation, compromise, settlement and defense and shall
have the right to select counsel with respect thereto, provided that the
Indemnifying Party shall promptly notify the Indemnified Party of all
developments in the matter. In no event shall the Indemnifying Party or
Indemnified Party compromise or settle any such matter without the prior
written consent of the other Party, which shall not be bound by any such
compromise or settlement absent its prior consent, which shall not be
unreasonably withheld or delayed. The Indemnified Party shall have the
right, but not the obligation, to be represented by counsel of its own
selection and at its own expense.
14.5. Nothing herein contained shall require an Indemnifying Party to carry out
any unlawful act or omission or which may lead to a judgment by default
being entered or executed against the Indemnifying Party.
14.6. Following the earliest Approval Date, Supplier agrees to maintain at its
expense sufficient product liability insurance in an amount not less than
* US dollars. Each party agrees to maintain all other insurances
reasonably necessary to provide sufficient cover for its legal and
statutory liabilities and any liabilities arising from this Agreement and
all insurable risks following use of the Substance and/or the Product and
to provide the other party with proof of such insurance upon written
request.
14.7. IN NO EVENT SHALL EITHER PARTY BE LIABLE TO THE OTHER PARTY UNDER THIS
AGREEMENT FOR INCIDENTAL, SPECIAL, CONSEQUENTIAL, INDIRECT, OR PUNITIVE
DAMAGES, INCLUDING, BUT NOT LIMITED TO, ANY CLAIM FOR DAMAGES BASED UPON
LOST PROFITS; PROVIDED, HOWEVER, THAT THIS LIMITATION WILL NOT LIMIT OR
RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY FOR
THIRD PARTY CLAIMS UNDER THIS CLAUSE 14 OR DAMAGES AVAILABLE FOR WILLFUL
OR INTENTIONAL BREACH BY EITHER PARTY OF THE CONFIDENTIALITY OBLIGATIONS
IN CLAUSE 16.
15. OTHER ACTIVITIES
15.1. Clinical Trial: As described in Clause 7.1 above, the parties agree and
undertake to enter into a clinical trial agreement with regard to a global
clinical trial of the Product, part of which will be conducted in
placecountry-regionIsrael. The Clinical Trial Agreement shall be attached
to this Agreement and, except as expressly described herein, shall be
considered an irrevocable part of this Agreement.
15
15.2. New Developments: Supplier shall inform Teva in writing if Supplier
initiates the clinical development of the Product for oncology indications
outside the Field (the "Development"). Teva shall have sixty (60) days
following receipt of such notice to inform Supplier of Teva's desire to
enter into an agreement to participate in the clinical trial and
distribution of the Product in such indications. If Teva provides such
notice, then the parties will begin discussions in good faith on the terms
and conditions of such participation and distribution, based on this
Agreement (including, without limitation, a section requiring Teva to fund
certain clinical trial activities, similar in spirit to the Clinical Trial
Agreement). The parties will agree to a number of patients as reasonable,
as required by the trial design and in accordance with the expected market
size and sales of the new Development.
16. CONFIDENTIALITY
16.1. Both parties agree and undertake that during the term of this Agreement
and thereafter, they shall keep confidential any and all Information
acquired in the course of the negotiation and performance and disclosed by
the other party hereunder, or which they acquire relating to the business,
finances or trade secrets of the other party and shall not disclose the
same or any part thereof to any third party.
16.2. Teva shall only use the Information for the purpose of the registration,
promotion, marketing and sale of the Product under this Agreement
(including any related trademarks or trade names). Supplier shall only use
Teva's Information for the purpose of performing its obligations under
this Agreement.
16.3. Both parties shall ensure that the Information is made available only to
the minimum number of its employees as reasonably necessary to perform its
obligations under this Agreement, and those consultants who have
undertaken in writing to preserve its confidentiality. The parties shall
make the employees and consultants aware of its obligations of
confidentiality under this Agreement and shall at all times procure
compliance by such employees and consultants thereunder.
16.4. The restrictions on use and disclosure of the Information hereunder shall
not apply to that part of the Information which either party is able to
demonstrate to the other:
16.4.1. is lawfully in the possession of the party receiving such
Information prior to the time of disclosure;
16.4.2. is, at the date of disclosure, public knowledge or becomes public
knowledge other than by the action of the party receiving such
information;
16.4.3. becomes available to the party receiving such Information from a
third party source and, to the best of the receiving party's
knowledge, was other than by reason of a breach by a party of its
obligations hereunder or a breach by any third party of an obligation
of confidentiality;
16
16.4.4. the disclosure of which is necessary or desirable to enable either
party to implement the provisions of this Agreement effectively,
provided that either party must specify details of the Information it
wishes to disclose and subject to third party's obligation to sign a
confidentiality agreement with terms at least as restrictive as in
this Agreement and obtain the other parties written consent to any
such disclosure, such consent shall not be unreasonably withheld;
16.4.5. that the information disclosed or used was independently developed
by the receiving party without reliance on the Information.
16.5. Notwithstanding the terms of Clauses 16.1 and 16.3, a party may disclose
Information of the other party to the extent such disclosure is required
under any law or regulation (including the regulation of any nationally
recognized securities exchange in accordance with the terms of Section
16.7); provided, that the minimum amount of information required to be
disclosed for the purposes of compliance with the said law or regulation,
shall be disclosed; and provided, further, that the party subject to such
requirement has, if legally permitted, informed the other party of such
requirement and, to the extent reasonably possible, permitted such other
party to seek confidential treatment or similar protection for such
Information.
16.6. On or after the Effective Date of this Agreement, at a mutually agreed
time, Supplier will issue a mutually agreed press release announcing the
existence of this Agreement, in the form, substance and schedule to be
mutually agreed upon by both parties in advance, and attached hereto as
Appendix E.
16.7. Neither party shall (i) publish, in whole or in part, information
regarding the existence or terms of this Agreement or (ii) use the other
party's name in any publication, except as otherwise approved in writing
by the other party. Notwithstanding the foregoing, each party may disclose
the existence and terms of this Agreement as necessary for filings with
the U.S. Securities Exchange Commission or a nationally recognized
securities exchange; provided, that such party informs the other party
prior to publication and receive the other parties approval (which shall
not be unreasonably withheld or delayed) and such party uses its
reasonable efforts to obtain confidential treatment for portions of this
Agreement as available, consults with the other party in connection with
such confidential treatment request, and permits the other party to
participate, to the greatest extent practicable, in seeking a protective
order or other confidential treatment. Teva shall use best efforts to
approve any such submission by Supplier within one (1) business day. The
publication of clinical data shall be subject to separate terms set forth
in the Clinical Trial Agreement
16.8. The provisions of this Clause 16 shall survive the expiration or
termination of this Agreement for any reason, for a period of ten (10)
years after such expiration or termination for any other Information.
17. TRADEMARKS
17.1. Supplier will select all Product Trademarks for use on or in connection
with Products, will be the sole owner of the Supplier House Marks and
Product Trademarks, will be responsible for the filing, prosecution,
maintenance and defense of all registrations of such trademarks, and will
17
be responsible for the payment of any costs relating to filing,
prosecution, maintenance and defense of such trademarks. Supplier shall
grant Teva a license to use such Product Trademarks and Supplier House
Marks solely for the marketing and distribution of the Products in the
Territory under this Agreement.
17.2. In the performance of this Agreement, Teva shall display such of
Supplier's trademarks and copyrighted material as approved by Supplier for
the Product. Any such use shall be in conformity with Supplier's written
instructions for the appearance and use of same. Teva shall provide
Supplier with exemplars and/or representative samples of any promotional
materials containing any Product Trademark or Supplier House Mark, prior
to using or disseminating such materials. Supplier shall have the right to
make reasonable objections to any such materials within ten (10) days of
its receipt of such copies on the grounds that Supplier believes in good
faith that the use of such materials will damage the reputation for
quality associated with the marks. Teva shall modify such promotional
materials in accordance with any such objections of Supplier. If no such
objections are received within the ten (10) days timeframe, the material
will be deemed accepted by Supplier. Teva's use of any Supplier House
Marks or Product Trademarks shall not give Teva any right to such
trademarks. Teva acknowledges and agrees that all use of such trademarks
and the goodwill generated thereby will inure solely to the benefit of
Supplier. Teva agrees not to use or file any application to register any
trademark or trade name in the Territory that is confusingly similar to
any Product Trademarks or Supplier House Mark, as interpreted by
applicable law in the Territory.
18. FORCE MAJEURE
18.1. The obligations of each party under this Agreement shall be suspended
during the period of this Agreement and to the extent that such party is
prevented or hindered from complying herewith by any cause beyond its
reasonable control including (insofar as they are beyond such control but
without prejudice to the generality of the foregoing expression) strikes,
lock-outs, labour disputes, act of god, war, riot, civil commotion,
malicious damage, compliance with any law or governmental order, rule,
regulation or direction, accident, breakdown of plant or machinery, fire,
flood, storm, difficulty or increased expense in obtaining workmen,
materials or transport or other circumstances affecting the supply of
goods or of raw materials therefore.
18.2. In the event of either party being so hindered or prevented, such party
shall give notice of suspension as soon as reasonably possible to the
other party stating the date and extent of such suspension and the cause
thereof. The failure to give such notice shall forfeit the rights of such
party to relief under this Clause.
18.3. Any party whose obligations have been suspended as aforesaid shall resume
the performance of such obligations as soon as reasonably possible after
the removal of the cause and shall so notify the other party. In the event
that such cause continues for more than six (6) consecutive months either
party may terminate this Agreement on thirty (30) days notice to the other
party.
18
19. GOVERNING LAW AND ARBITRATION
This Agreement shall be governed solely and exclusively by the substantive law
of the State of New York, U.S.A. Any dispute between the parties shall be
referred to arbitration to be conducted in accordance with the rules of the
International Chamber of Commerce, as amended from time to time. Such
arbitration shall be held in placeCityNew York, country-regionU.S.A. unless
otherwise agreed between the parties in writing. The parties agree that the
arbitration as aforesaid shall be conducted before a single arbitrator to be
agreed between the parties or failing agreement to be appointed in accordance
with the provisions of the arbitration rules referred to above The parties
further agree to exclude any right of application or appeal to any court arising
on the course of such arbitration and/or with respect to any award made in such
arbitration, which award shall be final and binding on the parties.
20. ENTIRE AGREEMENT; COUNTERPARTS
This Agreement constitutes the entire understanding between the parties hereto
with respect to the subject matter hereof and supersedes all prior agreements,
negotiations and discussions between the parties hereto relating thereto. This
Agreement may be executed by facsimile and in two or more counterparts, each of
which shall be deemed an original and all of which shall together constitute one
and the same instrument.
21. EXECUTION AND DELIVERY OF THIS AGREEMENT
21.1. Supplier hereby represents and warrants that the execution and delivery by
Supplier of this Agreement and the performance by Supplier of its
obligations hereunder have been duly authorized by all necessary corporate
action on the part of Supplier, and do not conflict with the terms of any
other contract, agreement, arrangement or understanding to which Supplier
is a party.
21.2. Teva hereby represents and warrants the execution and delivery by Teva of
this Agreement and the performance by Teva of its obligations hereunder
have been duly authorized by all necessary corporate action on the part of
Teva, and do not conflict with the terms of any other contract, agreement,
arrangement or understanding to which Teva is a party.
22. INDEPENDENT CONTRACTORS
The relationship of the parties is that of independent contractors. Except as
set out in this Agreement nothing shall constitute the parties as joint ventures
or co-owners or constitute either party as the agent, employee or representative
of the other or empower either party to act for, bind or otherwise create or
assume any obligation on behalf of the other.
23. AMENDMENTS
No amendment or variation of this Agreement shall be effective unless in writing
and signed by duly authorised representatives of the parties.
19
24. ASSIGNMENT
Neither party shall without the prior written consent of the other party,
assign, sub-licence, sub-contract, delegate, charge or part with or otherwise
dispose of this Agreement or the benefit thereof or any right or obligation
hereunder or grant any sub-licence or sub-contract, save that (a) Teva shall be
entitled to designate one or more of its Affiliates in the various countries
comprising the Territory, to implement and carry out Teva's obligations in the
countries, and (b) either party may assign or transfer this Agreement or any of
its rights or obligations hereunder without such consent to (i) any Affiliate of
such party, or (ii) to any third party with which it merges or consolidates, or
to which it transfers all or substantially all of its assets to which this
Agreement relates. The assigning party (except if it is not the surviving
entity) will remain jointly and severally liable with the relevant Affiliate or
third party assignee under this Agreement, and the relevant assignee or
surviving entity will assume in writing all of the assigning party's obligations
under this Agreement. Any party that desires to make an assignment described in
clause (b) above will provide the other party with advance written notice of
such assignment and will consider in good faith any comments provided by such
other party. In the event of an assignment by Supplier, if Teva is barred by
applicable laws from doing business with the assignee or if Teva otherwise
demonstrates that such assignment presents a strategic or ethical conflict of
interest that would materially affect Teva's ability to conduct its obligations
under this Agreement, then within thirty (30) days following such assignment,
Teva may terminate this Agreement upon written notice to Supplier.
25. SEVERABILITY
The invalidity or unenforceability of any term of or any right arising pursuant
to this Agreement shall not in any way affect the remaining terms or rights and
Supplier and Teva hereby each undertakes to use all reasonable endeavours to
replace any legally unenforceable provision with (as far as practicable)
provisions which will effect for the parties the same commercial results as were
intended by the original provisions.
26. WAIVER
The failure of a party hereto to exercise or enforce any right under this
Agreement shall not be deemed to be a waiver thereof nor operate so as to bar
the exercise or enforcement thereof at any time or times thereafter.
27. CONVENTION ON CONTRACTS FOR THE INTERNATIONAL placeCitySALE OF GOODS
To the extent that it may otherwise be applicable, the parties hereby expressly
agree to exclude from the operation of this Agreement, the United Nations
Convention on Contracts for the International Sale of Goods, concluded at
placeCityVienna, on dateYear1980Day11Month4April 11th 1980, as amended and as
may be amended further from time to time.
28. NOTICES
All notices shall be in writing and shall be given by delivery by hand, air
courier or transmission by fax to the address or fax number of the relevant
party set out at the beginning of this Agreement or such other address or fax
number as either party may notify to the other from time to time and shall be
addressed to the representatives of the parties set out below;
20
If to Supplier:
CEL-SCI Corporation
8229 Boone Boulevard, Suite 802
Vienna, VA 22182, USA
Attention: Geert Kersten
Telephone: (703) 506-9460
===============
Facsimile: (703) 506-9471
================
If to Teva:
Teva Pharmaceutical Industries Limited
Hatrufa St. 12, Kiryat Nordau
Sapir Industrial Zone, Natanya, PoB 8077
Israel
Attention: Efrat Klachevsky
Telephone: *
Facsimile: *
The parties shall inform the other within 7 days of any change in address or fax
number. Any such notice given as aforesaid shall be deemed to have been given at
the time of delivery (if delivered by hand or air courier) or completion of
transmission (if sent by fax).
[Signature page follows.]
21
IN WITNESS WHEREOF, the parties have by duly authorized persons, executed
this Agreement, as of the date first above written.
TEVA PHARMACEUTICAL CEL -SCI CORPORATION
INDUSTRIES LTD.
Name: Judith Vardi Name: Geert R. Kersten
------------------------------ ----------------------------
Title: Vice President, Israel, Title: Chief Executive Officer
Mediterranean, Africa and Turkey
Signature: /s/ Judith Vardi Signature: /s/ Geert R. Kersten
------------------------- ------------------------
Name: Efrat Klachevsky Name:
------------------------------ ----------------------------
Title: Director, Business Development, Title:
Israel, Mediterranean, Africa and
Turkey
Signature: /s/ Efrat Klachevsky Signature:
------------------------- ------------------------
Date: 07/08/08 Date:
------------------------------ ----------------------------
List of Appendices:
Appendix A - Product Description
Appendix B - Specifications
Appendix C - Pharmacovigilance Agreement
Appendix D - Clinical Trial Agreement
Appendix E - Press Release Announcement
22
CONFIDENTIAL
CONFIDENTIAL
EXCLUSIVE LICENSE AND DISTRIBUTION AGREEMENT
APPENDIX A
Description of: "the Product"
Product description:
*
The remainder of this page has been left blank intentionally
EXCLUSIVE LICENSE AND DISTRIBUTION AGREEMENT
APPENDIX B
"the Specifications" (of the Product)
CEL-SCI CORPORATION
STANDARD SPECIFICATION NUMBER
*
*
*
STANDARD SPECIFICATION
LEUKOCYTE INTERLEUKIN, INJECTION
*
*
*
*
INTERIM
STANDARD SPECIFICATION
LEUKOCYTE INTERLEUKIN, INJECTION
ACCEPTANCE CRITERIA:
* * *
* * *
* * *
* *
* *
* *
* *
* * *
* * *
* * *
* *
*
INTERIM
STANDARD SPECIFICATION
LEUKOCYTE INTERLEUKIN, INJECTION
ACCEPTANCE CRITERIA (continued):
* * *
* * *
* * *
* * *
* * *
* * *
* * *
* * *
-------------------------------------------------------------------------------
APPENDIX C
A Phase III, Open-label, Randomized, Multi-center Study of the Effects of
Leukocyte Interleukin, Injection [Multikine(R)] Plus
Standard of Care (Surgery +Radiotherapy or Surgery + Concurrent
Chemoradiotherapy)in Subjects with Advanced Primary Squamous Cell Carcinoma
of the Oral Cavity Versus Standard of Care Only
A Phase III, Open-label, Randomized, Multi-center Study of the Effects of
Leukocyte Interleukin, Injection [Multikine(R)] Plus Standard of Care
(Surgery + Radiotherapy or Surgery + Concurrent Chemoradiotherapy)
in Subjects with Advanced Primary Squamous Cell Carcinoma of
the Oral Cavity Versus Standard of Care Only
Regulatory Sponsor: CEL-SCI Corporation
8229 Boone Boulevard
Suite 802
Vienna, Virginia 22182 U.S.A.
Phone: 703-506-9460 Fax: 703-506-9471
CEL-SCI Corporation
Funding Sponsor: 8229 Boone Boulevard
Suite 802
Vienna, Virginia 22182 U.S.A.
Phone: 703-506-9460 Fax: 703-506-9471
Study Product: Leukocyte Interleukin, Injection [Multikine(R)]
* *
* *
*
*
* *
* *
*
*
Table 1 *
*
*
Figure 1
Figure 2. Cell cycle marker (Ki67) in Multikine(R) treated Oral Squamous Cell
Carcinoma (OSCC)
A. Morphometry of Ki-67+ cells in OSCC. B. Visualization of
Data are means +/-SEM, *p<0.05 in OSCC by Ki-67+(Histopathology)
0= Control Untreated Group
Figure 3. Histological appearance of necrosis in oral squamous cell carcinoma
(H&E staining)
Panel A Panel B
Panel A: Control - Lack of necrosis in the epithelial nests of Oral Squamous
Cell Carcinoma.
Panel B: Multikine(R) treatment - Entire cancer nest is necrotic
and filed with debris and leukocytes.
*
*
*
(1) Saunders, M.I., Rojas, A..M, Management of Cancer of the Head and Neck-A
Cocktail with your PORT? N Engl J Med. 2004; 350: 1997-1999. (2) .Vokes, E. E.,
Weichselbaum, R.. R., Lippman, S.C., Hong, W. K. Head and neck cancer. N Engl J
Med. 1993; 328: 184-194.
(3) Oral Cancer Background Papers Prepared for the National Strategic planning
Conference for the Prevention and control of Oral and pharyngeal Cancer, August
7-9, 1996 Working Draft, Chapter I, Descriptive Epidemiology, I-1.
(4) Seer Cancer Statistics Review 1975-2002, Table XXX-12.
(5) Forastiere, A. A., Trotti, A., Pfister, D. G., Grandis, J. R. Head and neck
cancer: recent advances and new standards of care.. J. Clin. Oncol. 2005;24:
2603-2605. (6) Hitt R.., Paz-Ares L., Brandariz A., Castellano D., Pena C.,
Millan J.M., Calvo F., Ortiz de Urbina D., Lopez E., Alvarez-Vicent J.J.,
Cortes-Funes HInduction. chemotherapy with paclitaxel, cisplatin and
5-fluorouracil for squamous cell carcinoma of the head and neck: long-term
results of a phase II trial. Ann Oncol. 2002;13:1665-1673. (7) Monnerat C.,
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Appendix D- Clinical Trial Agreement
[See attched]
1
CLINICAL TRIAL MANAGEMENT SERVICES AGREEMENT
Between
TEVA PHARMACEUTICAL INDUSTRIES LIMITED
A limited liability company incorporated
under the laws of Israel, of 5 Basel
Street, Petah Tiqva 49131, Israel
("Teva")
And
CEL-SCI CORPORATION
a company incorporated under the laws of the
USA, of 8229 Boone Boulevard, Suite 802,
Vienna, VA 22182, USA
("the Company")
WHEREAS the Company has developed an Immunotherapy for cancer - Multikine
(Leukocyte Interleukin) injection (the "Drug"), and is interested in evaluating
the safety, tolerability and efficacy of the Drug in a Phase III Trial in
patients with Squamous Cell carcinoma of the oral cavity; and
WHEREAS Teva and the Company have entered into an Exclusive License and
Distribution Agreement dated of even date herewith (the "Distribution
Agreement") in which Teva receives the right to market and distribute the Drug
in certain territories; and
WHEREAS the Company wishes to engage Teva to manage and monitor one or more
clinical trials involving the Drug in Israel as set forth and described in
Appendix A hereto (the "Trial"), all in accordance with the terms and conditions
set out herein and the relevant laws and regulations; and
WHEREAS Teva is experienced in managing and monitoring clinical trials and is
willing to assist the Company by managing and monitoring the Trial, all in
accordance with the terms and conditions set out herein.
THEREFORE THE PARTIES AGREE AS FOLLOWS:
1. INTERPRETATION
1.1. The preamble to this Agreement forms an integral part hereof.
1.2. Section headings in this Agreement are intended solely for convenience
of reference and shall be given no effect in the interpretation of
this Agreement. All signed appendices to this Agreement, whether
attached at the time of signature hereof or at any time thereafter,
shall be construed as an integral part of this Agreement.
1.3. In this Agreement, the following expressions shall bear the meanings
assigned to them below and cognate expression shall bear corresponding
meanings.
1
1.3.1. "Commencement Date" shall mean the date on which both parties
have signed this Agreement.
1.3.2. "Global CRO" shall mean the entity to be selected and retained
by the Company following the date hereof to oversee the
performance of the worldwide Phase III clinical trial of which
the Trial to be conducted hereunder is a part. Upon signing the
agreement between Company and Global CRO, a notice will be sent
to Teva informing Teva of the Global CRO's name and contact
details.
1.3.3. "Protocol" shall mean the protocol, as written and provided to
Teva by the Company, attached as Appendix A to this Agreement.
1.3.4. "Trial Activities" shall mean the list of items agreed upon
between the parties and to be paid by Teva, for the performance
of the Trial Management Services, as defined below, set out in
Appendix B to this Agreement.
1.3.5. "Study Team" shall mean the team that will supervise and
monitor the performance of the Trial.
1.4. In this Agreement, "including" and "includes" means including, without
limiting the generality of any description preceding such terms.
2. APPOINTMENT OF TEVA
For the portion of the Trial to take place in Israel, the Company hereby
appoints Teva to provide the clinical management and supervision services of
the Trial as set out in this Agreement and in Appendix C (the "Trial
Management Services") subject to the Company fulfilling its obligations as
set out in this Agreement and in Appendix C, whether to be performed by Teva
directly or through a third party, in accordance with the terms and
conditions of this Agreement, and the relevant laws and regulations, and
Teva hereby accepts such appointment.
3. OBLIGATIONS OF TEVA
3.1. Teva shall ensure that the Trial Management Services shall be carried
out in accordance with:
3.1.1. The provisions of the Protocol and the other terms of this
Agreement; and
3.1.2. The reasonable written guidelines and instructions provided by
the Company and the Global CRO (including any Global CRO standard
operating procedures) for the conduct of the Trial (provided that
Teva shall use its best efforts to comply with the Global CRO's
guidelines and shall notify the Company immediately in the event
2
that it believes that any such written guideline or instruction
is unreasonable and the parties shall promptly meet and discuss
any such concern); and
3.1.3. The relevant laws, regulations, guidelines and ethical
requirements prevailing in the country in which the Trial is
carried out.
3.2. Teva undertakes to perform the Trial Management Services in a
professional and workmanlike manner, and devote the necessary
personnel and all other resources necessary to perform the Trial
Management Services.
3.3. Teva shall make the Study Team aware of relevant provisions of this
Agreement and shall ensure compliance therewith by the Study Team.
3.4. Teva shall keep appropriate records relating to the Trial in
connection with the performance of the Trial Management Services in
accordance with the Protocol and applicable laws, regulations and
guidelines.
3.5. Teva shall keep the Global CRO informed of the progress of the Trial.
Teva will provide the Company with written monthly progress reports
that will include the status of and issues raised by any Trial site
and a summary of any reported adverse events. Teva will provide to the
Company reports of Teva's monitoring visits to any site or
investigator on a timely basis as specified in Appendix C.
3.6. Teva shall permit representatives of the Company or, alternatively,
the Global CRO, as applicable to examine relevant data, documents, and
records of Teva pertaining to the Trial Management Services, in order
to verify compliance by Teva with its obligations under this
Agreement. Such audit activities shall be coordinated with Teva in
advance and conducted during regular business hours. The Company will
use reasonable efforts to coordinate with the Global CRO to minimize
duplication of any such examinations and in no event should there be
more than one (1) examination a month by the Company and the Global
CRO, and the Company will cooperate with Teva to address any
reasonable objections to the timing and frequency of inspections
requested by both the Company and the Global CRO.
3.7. Teva shall perform its obligations in accordance with the list of
responsibilities attached hereto as Appendix C.
3.8. In the event that the Israeli laws and regulations applicable to the
manufacture, labeling or supply of Drug for use in the Trial differ
substantially from the applicable laws and regulations of the United
States of America or the European Union, and in the event that Teva is
aware of such, then Teva shall inform the Company in writing of such
differences.
3
3.9. At its sole discretion, the Company may amend the Protocol, and, upon
the Company's request, Teva will assist the Company in making such
modifications. An amended Protocol will supersede the previous
versions. The Company will notify Teva of any modification of a
Protocol or the Trial. Within ten (10) business days from Teva's
receipt of notice of such modification, Teva will provide the Company
with its opinion as to the alterations consequences and an estimate of
the reasonable alterations to the Trial timeline and Trial Activities
(whether an increase or decrease) directly resulting from such
modification. The Company will have ten (10) business days to approve
such estimates. If the Company does not approve a modification
estimate and has not terminated the Trial, but wants the Trial to be
modified to include such modification, each party will use its good
faith efforts to agree on modification estimates that are commercially
reasonable and mutually acceptable. At the Company's request, Teva
shall continue performing Trial Management Services for the Trial
without implementing the proposed modifications unless and until the
parties have reached agreement regarding a revised estimate of the
timeline and budget based upon the proposed modifications. For the
avoidance of doubt it is hereby clarified that the Company shall be
responsible for any and all increased costs associated with any
amendments to the Protocol or the Trial in existence on the date
hereof, provided that any increased costs shall be offset, if
applicable, by any cost savings or reductions for eliminated or
reduced activities (with no refund right for costs already paid).
4. OBLIGATIONS OF THE COMPANY
4.1. The Company shall supply the Drug for the Trial, at Teva's expense, as
agreed upon in section 7 of the Distribution Agreement and further
detailed in section 5 below, and according to the timetables,
quantities, and specifications as indicated in the Protocol.
4.2. The Company, either directly or through the Global CRO, shall provide
Teva with all the relevant articles or information required for the
performance of the Trial Management Services.
4.3. The Company shall perform its obligations in accordance with the list
of responsibilities, attached hereto as Appendix C.
4.4. In addition to all other obligations set forth in this Agreement, the
Company warrants that it shall act as a sponsor of the Trial, in the
meaning ascribed to it in the Israeli Ministry of Health guidelines.
4.5. The Company shall hold and maintain, throughout the term of this
Agreement, and for a sufficient time thereafter, sufficient insurance
to cover all the requirements of the local laws and regulations,
including without limitation, insurance to cover all patients taking
part in the Trial, as per the requirements of the Ministry of Health
in Israel.
4
5. PAYMENT
Teva shall fund, at its cost, the performance of certain activities
related to the Trial to be conducted in Israel, * provided that Teva shall
be obligated to use best efforts to enroll * patients in accordance with
the list of activities comprising the Trial Activities for such patients.
6. STUDY TEAM
Teva shall establish the Study Team in consultation with the Company. The
function of the Study Team shall be to manage and monitor the Trial in
accordance with Appendix A and the terms of this Agreement.
7. WARRANTIES AND REPRESENTATIONS
7.1. Teva warrants and represents that it has the experience, capability,
qualified personnel and resources to perform the Trial Management
Services under this Agreement.
7.2. The Company warrants and represents that it is the sole and exclusive
owner of the Drug and that Teva is not and will not, in any event, be
liable for any claims, actions and suits arising as a result of the
use, safety and quality of the Drug, subject to the indemnity
obligations set forth in Section 11.
7.3. The Company warrants that, to the Company's knowledge as of the
Commencement Date, applicable national and local laws do not prohibit
the conduct of the Trial carried out in accordance with the Protocol.
7.4. In addition, each party warrants and represents, that it shall perform
all of its obligations under this Agreement (including, in the case of
the Company, the manufacture, labeling and supply of Drug for use in
the Trial), in accordance with the applicable rules, regulations and
guidelines in Israel. The Company, as sponsor of the Trial, warrants
and represents that it shall perform all of its obligations under this
Agreement according to the rules, regulations and guidelines set forth
with respect to the sponsor of a clinical trial by the Ministry of
Health in Israel.
7.5. Each party hereby warrants and represents that it has the power and
authority and the legal right to enter into this Agreement to perform
its obligations hereunder, and has taken all necessary action on its
part to authorize the performance of such obligations.
7.6. Teva warrants that it has not, and shall not, employ, contract with,
or retain any person directly to perform services under this Agreement
if such a person is, to the best of Teva's Knowledge (with the use of
reasonable efforts to investigate), debarred or disqualified by any
applicable regulatory or governmental authority from performing the
obligations requested by Teva.
5
7.7. For the avoidance of doubt it is hereby clarified and acknowledged by
the Company that Teva does not make any warranty as to the results,
conclusions or reports, including without limitation, the Results, as
defined below, of the Trial Management Services and/or the Trial to
be: (i) useful to the Company, (ii) in compliance with the Company's
expectations, and/or (iii) of any commercial value whatsoever.
7.8. The Company hereby represents and warrants that, to the best of its
knowledge as of the date hereof, the conduct of the Trial in
accordance with the Protocol and/or the Trial Management Services will
not constitute an infringement of the intellectual property rights
(that relate to the Product) of any third party.
7.9. Except as otherwise expressly set forth in this Agreement, neither the
Company nor Teva makes any representations or extends any warranties
of any kind, either express or implied, including any express or
implied warranties of merchantability or fitness for a particular
purpose.
8. TERM AND TERMINATION
8.1. All of the provisions of this Section 8, or any other right of the
parties to terminate, shall be subject to the overriding consideration
that this Agreement pertains to the carrying out of a clinical trial,
and the interests and safety of the participants in the Trial shall
take precedence over all of the rights of the parties to terminate.
8.2. This Agreement shall commence on the Commencement Date and, subject to
prior termination in accordance with the other terms of this
Agreement, shall terminate upon the completion of the Trial Management
Services.
8.3. The Company shall be entitled to terminate this Agreement by providing
Teva with sixty (60) days prior written notice, without penalty or
liability therefore or the payment of any compensation.
8.4. Teva shall be entitled to terminate this Agreement by written notice
to the Company, effective immediately, if in the reasonable opinion of
Teva the continuation of the Trial represents an unacceptable risk to
the participants or is contrary to accepted medical practice.
8.5. Either party shall be entitled to terminate this Agreement by giving
thirty (30) days written notice to the other, effective immediately,
upon any of the following events:
6
8.5.1. The other party commits a material breach of this Agreement
which, in the case of a breach which is capable of remedy, shall
not have been remedied within thirty (30) days of the receipt by
the party in default of a notice identifying the breach requiring
its remedy.
8.5.2. The other party is unable to pay its debts or enters into
compulsory or voluntary liquidation (other than for the purpose
of affecting a meeting of its creditors) or has an administrator
appointed over all or any part of its assets; provided, in each
case, that such proceedings are not dismissed within ninety (90)
days.
8.6. Termination of this Agreement for any reason shall not affect any of
the rights and obligations of the parties which shall have accrued
prior to the effective date of termination.
8.7. This Agreement shall survive the termination of the Distribution
Agreement, for any reason whatsoever, unless otherwise terminated in
accordance with this Section 8.
8.8. Sections 4.4, 7.7, 7.8, 8.6, 8.7, 8.8, 9, 10, 11, 12, 18 and 20 shall
survive termination or expiration of this Agreement for any reason.
9. CONFIDENTIALITY
9.1. Teva shall keep secret and confidential, during the term and for a
duration of ten (10) years from the expiration or termination of this
Agreement, all confidential and/or proprietary information supplied by
the Company, whether in written, oral, electronic or any other form,
including without limitation, all information relating to the Drug,
the Trial, the Results (as defined in Section 10.1 below) and the
Trial Management Services ("Information") and shall not disclose or
use the Information other than for the purposes of exercising its
rights or fulfilling its obligations pursuant to this Agreement or the
Distribution Agreement, including the performance of Trial Management
Services, which shall include: (i) disclosure to the relevant hospital
authorities or ethical review committee, if such disclosure is
necessary in order to obtain the required approvals for the conduct of
the Trial and/or the performance of the Trial Management Services;
(ii) disclosure to those of Teva's directors, officers, employees,
agents, and consultants who have a "need to know" such information for
the performance of the Trial Management Services and/or in the
fulfillment of its obligations hereunder, provided that the
aforementioned are bound by obligations of confidentiality and non-use
similar to those set out herein. Teva agrees that it shall take
commercially reasonable steps to prevent the disclosure or use of the
Company's Information by its directors, officers, employees, agents
and consultants except as expressly provided in this Agreement.
7
9.2. The provisions of Section 9.1 shall not apply to:
9.2.1. Information which is known to the receiving party prior to
disclosure by the disclosing party, as shown by written records;
9.2.2. Information which is or becomes public knowledge through no
fault of the receiving party, or its employees, who have been
exposed to the Information;
9.2.3. Information which is disclosed to the receiving party by a
third party;
9.2.4. Information which is required by law, court or any competent
authority to be disclosed, provided that, if legally permitted,
the receiving party shall notify the disclosing party thereof, in
order to enable the disclosing party to seek an appropriate
protective order or other reliable assurance that confidential
treatment shall be accorded to such Information (with the
receiving party's assistance, if necessary), and such disclosure
shall be made to the minimum extent required;
9.2.5. Information which is independently developed by the receiving
party, or any of its employees, agents, consultants or other
representatives, without the use of or reliance upon the
Information.
9.3. The parties undertake to maintain the confidentiality of all details
relating to the participants in the Trial in accordance with all
applicable laws, regulations and guidelines governing the
confidentiality and privacy of individually identifiable health
information.
9.4. Upon termination of the Trial and/or the Trial Management Services, or
upon the written demand of the other party, each of the parties shall
return the other party's Information, and all copies or other
manifestations thereof, keeping only one copy of such Information in a
safe location as a record of its obligations hereunder.
9.5. Neither party shall use the other's name in any marketing,
advertising, press release or other promotional literature or any
other publicity without the other's prior written consent, with regard
to the wording and timing of the release, all except for any mention
in any applications to official authorities for regulatory approvals,
or in the fulfillment of any duty owed to any competent authority
(including a duty to make regulatory filings and/or reports).
Notwithstanding anything to the contrary, Company may refer to Teva as
its contract research organization in the Territory as required under
applicable laws, regulations and Ministry of Health guidelines.
8
10. COPYRIGHT AND OWNERSHIP OF RESULTS
10.1. All inventions (patentable or not), discoveries, improvements,
reports, data and other results developed or generated by or on behalf
of Teva during and/or arising from the performance of the Trial
Management Services (collectively "Results"), and all intellectual
property directly related thereto, shall be the sole and exclusive
property of the Company and the Company shall be free to use the
Results as it sees fit. Teva agrees to assign, and does hereby assign
to the Company, all of Teva's right, title and interest in and to the
Results. For the removal of doubt the publication of any of the
Results in any scientific or other publication or presentation shall
be within the Company's sole discretion, provided that the Company
shall not, in any such publication and/or in any event, mention Teva's
name and/or the existence and/or the terms and conditions of this
Agreement, without complying with the terms of Section 9.5.
10.2. If further documents or actions are necessary for the purpose of
confirming or to vest in the Company's rights, title or interest in
and to the Results pursuant to Section 10.1 above, Teva agrees to
execute such documents and to take such reasonable actions as are
necessary to confirm or to vest such rights, title or interest, at the
Company's sole expense.
10.3. Notwithstanding the foregoing, both parties acknowledge that all
computer programs, applications, databases, techniques, methods,
models, processes and the like used by the Study Team in performance
of the Trial Management Services under this Agreement remain the
exclusive property of the party supplying the foregoing property.
10.4. Teva acknowledges that any and all quantities of the Drug shall
remain the sole and exclusive property of the Company. Upon
termination of this Agreement for any reason, all remaining quantities
of the Drug in Teva's possession or control shall be returned to the
Company at the Company's sole expense and the Company shall refund
Teva for Teva's pro rata landed costs of the Drug not used in the
Trial and/or Trial Management Services, except in the event that the
remaining Drug is required according to any laws and/or regulations,
including without limitation, of the Israeli Ministry of Health
guidelines.
10.5. Nothing contained herein shall be deemed to grant Teva a licence to
use the Drug or the Results for any purposes whatsoever, except for
the performance of the Trial Management Services hereunder.
11. LIABILITY AND INDEMNITY
11.1. Teva shall indemnify and hold harmless the Company, and the Company's
affiliates, officers, directors and employees (each a "The Company
9
Indemnified Party"), from any and all damages, losses, liabilities,
claims including without limitation, claims for bodily injury or
death, and reasonable attorney fees (collectively, "Liabilities") to
the extent that such Liabilities arise from a third party claim based
upon: (i) the gross negligence or willful misconduct of Teva or of any
officers, directors or employees of Teva; (ii) any material breach of
this Agreement by Teva or any other person for whose actions Teva is
liable under applicable law; and/or (iii) the violation by Teva, or
any of its directors, officers or employees, of the applicable law or
other governmental requirement, which shall directly arise as a result
of the Trial Management Services performed by Teva, according to this
Agreement, provided; however, that the above indemnification
obligations shall not apply to the extent that any Liabilities arise
out of: (i) any breach of this Agreement, relating to the cause of the
Liabilities, by the Company or any other person for whose actions the
Company is liable under applicable law; (ii) any violation by any the
Company Indemnified Party of applicable law or other governmental
requirement, relating to the cause of the Liabilities; or (iii) the
gross negligence or willful misconduct of any the Company Indemnified
Party, relating to the cause of the Liabilities.
11.2. The Company shall indemnify and hold harmless Teva, and Teva's
affiliates, officers, directors and employees (each a "Teva
Indemnified Party"), from any and all Liabilities, to the extent that
such Liabilities arise from a third party claim based upon: (a) the
performance by Teva of the Trial Management Services in accordance
with this Agreement and/or as a result of any instructions received by
the Company; (b) any material breach of this Agreement by the Company
or any other person for whose actions the Company is liable under
applicable law; (c) the negligence or willful misconduct of the
Company or of any directors, officers or employees of the Company; and
(d) the use of the Drug by Teva and/or the Study Team, during the
performance of the Trial and/or the Trial Management Services and/or
(e) the use of the Drug by the hospitals and/or centers and/or the
investigator, during the performance of the Trial; (f) the violation
by the Company, its directors, officers or employees of the applicable
law or other governmental requirement, provided; however, that the
above indemnification obligations shall not apply to the extent that
any Liabilities arise out of: (i) any breach of this Agreement,
relating to the cause of the Liabilities, by Teva or any other person
for whose actions Teva is liable under applicable law; (ii) any
violation by a Teva Indemnified Party of applicable law or other
governmental requirement, relating to the cause of the Liabilities; or
(iii) the gross negligence or willful misconduct of a Teva Indemnified
Party, relating to the cause of the Liabilities.
11.3. If any the Company Indemnified Party or Teva Indemnified Party (such
party an "Indemnified Party") receives notice of any claim or action
for which indemnity may be sought from the relevant indemnifying party
pursuant to this Section 11 above, such indemnifying party shall be,
as soon as reasonably possible, notified thereof in writing. The
indemnifying party shall have sole control over the defence and
10
settlement of such claim and the Indemnified Party shall not be
entitled to settle or compromise such claim or action without the
prior written consent of the indemnifying party and shall reasonably
cooperate with the indemnifying party in the investigation and defence
of such claim or action, provided that in any event the indemnifying
party shall use its best efforts to ensure that the good name and
reputation of the Indemnified Party remains intact . The Indemnified
Party may employ its own counsel if it wishes to do so, at its sole
expense.
11.4. IN NO CASE SHALL EITHER PARTY BE LIABLE FOR ANY INDIRECT, SPECIAL,
INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF, OR IN CONNECTION
WITH, THIS AGREEMENT; PROVIDED HOWEVER THAT THIS LIMITATION WILL NOT
LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER
PARTY FOR THIRD PARTY CLAIMS OR DAMAGES AVAILABLE FOR WILLFUL OR
INTENTIONAL BREACH BY EITHER PARTY OF THE CONFIDENTIALITY OBLIGATIONS
IN ARTICLE 9.
12. INSURANCE
12.1. The parties shall hold and maintain, throughout the term of this
Agreement, and for a sufficient time thereafter, sufficient insurance
to cover any and all of their liabilities pursuant to this Agreement,
including without limitation, insurance as mentioned in Section 4.5.
12.2. The parties shall provide to one another certificates evidencing the
holding and maintenance of such insurances upon the request of the
other party. 13. APPROVALS
Teva shall obtain and maintain all authorizations and approvals (if any)
required from the appropriate regulatory authorities and the relevant ethics
committees and other scientific bodies for the performance of the Trial and
the Trial Management Services.
14. ASSIGNMENT
Neither party shall without the prior written consent of the other party,
assign, sub-license, sub-contract, charge or part with or otherwise dispose
of this Agreement or the benefit thereof or any right or obligation
hereunder or grant any sub-license or sub-contract, save that (a) Teva shall
be entitled to designate one or more of its Affiliates in Israel, to
implement and carry out Teva's obligations under this Agreement, and (b)
either party may assign or transfer this Agreement or any of its rights or
obligations hereunder without such consent to (i) any Affiliate of such
party, or (ii) to any third party with which it merges or consolidates, or
to which it transfers all or substantially all of its assets to which this
Agreement relates. The assigning party (except if it is not the surviving
11
entity) will remain jointly and severally liable with the relevant Affiliate
or third party assignee under this Agreement, and the relevant assignee or
surviving entity will assume in writing all of the assigning party's
obligations under this Agreement. Any party that desires to make an
assignment described in clause (b) above will provide the other party with
advance written notice of such assignment and will consider in good faith
any comments provided by such other party. In the event of an assignment by
the Company, if Teva is barred by applicable laws from doing business with
the assignee or if Teva otherwise demonstrates that such assignment presents
a strategic or ethical conflict of interest that would materially affect
Teva's ability to conduct its obligations under this Agreement, then within
thirty (30) days following such assignment, Teva may terminate this
Agreement upon written notice to the Company.
15. SEVERABILITY
Should any part or provision of this Agreement be held unenforceable or in
conflict with the applicable laws or regulations of any jurisdiction, the
invalid or unenforceable part or provision shall, provided that it does not
go to the root of this Agreement, be replaced with a revision which
accomplishes, to the extent possible, the original business purpose of such
part or provision in a valid and enforceable manner, and the balance of this
Agreement shall remain in full force and effect and binding upon the parties
hereto.
16. ENTIRE AGREEMENT/AMENDMENT/WAIVER
16.1. This Agreement embodies and sets forth the entire agreement and
understanding between the parties hereto and supersedes all prior oral
and written agreements relating to the subject matter of this
Agreement. Neither party shall be entitled to rely on any agreement,
understanding or arrangement not expressly set forth in this
Agreement.
16.2. This Agreement (including, for the removal of doubt, the Appendices
hereto) shall not be amended, modified, varied or supplemented except
in writing signed by duly authorized representatives of the parties
hereto.
16.3. No failure or delay on the part of either party hereto to exercise
any right or remedy under this Agreement shall be construed or
operated as a waiver thereof nor shall any single or partial exercise
of any right or remedy as the case may be. The rights and remedies
provided in this Agreement are cumulative and are not exclusive of any
rights or remedies provided by law.
17. RELATIONSHIP OF THE PARTIES
The relationship of the parties is that of independent contractors. Except
as set out in this Agreement, nothing shall constitute the parties as joint
ventures or co-owners or constitute either party as the agent, employee or
representative of the other or empower either party to act for, bind or
otherwise create or assume any obligation on behalf of the other.
12
18. GOVERNING LAW
The agreement shall be governed by, and construed in accordance with, the
laws of the State of New York, USA, without giving effect to its principles
of conflicts of law. Each of the parties hereto hereby irrevocably submits
to the jurisdiction of the courts of competent jurisdiction located in the
State of New York, USA for the settlement of any dispute under or in
connection with this agreement.
19. FORCE MAJEURE
Each of the parties hereto shall be excused from the performance of its
obligations hereunder, in the event that such performance is prevented by
Force Majeure (as defined below) provided that the party claiming Force
Majeure shall: (i) give notice in writing to the other party without undue
delay after such circumstance has occurred; and (ii) use its best efforts to
avoid or remove such cause of non-performance and shall fulfill and continue
performance hereunder with the utmost dispatch whenever and to the extent
that such cause or causes are removed or cease to exist. For the purpose of
this Agreement, "Force Majeure" is defined as follows: causes beyond the
control of either of the parties, including but not limited to, acts of God,
acts, regulations or laws of any government, war, civil commotion,
destruction of production facilities or materials by fire, earthquake or
storm, labour disturbances, epidemic and failure of public utilities or
common carriers.
20. NOTICES
Any payment, notice and other written communications required or permitted
to be made or given may be made or given by either party by facsimile with
confirmed transmission; by first-class mail, postage prepaid; or by courier
to the mailing address or facsimile numbers set as below:
If to Teva:
Teva Pharmaceutical Industries Limited
Hatrufa St. 12, Kiryat Nordau
Sapir Industrial Zone, Natanya, PoB 8077
Israel
Attention: Dr. Coby Mazliah
Telephone: *
Facsimile: *
13
If to the Company:
CEL-SCI Corporation
8229 Boone Boulevard, Suite 802
Vienna, VA 22182, USA
Attention: John Cipriano
Telephone: (703) 506-9460
Facsimile: (703) 506-9471
Or to such other addresses or facsimile numbers as either Party shall
designate by notice, similarly given, to the other Party. Notices or written
communications shall be deemed to have been sufficiently made or given: (i)
if mailed, seven (7) days after being dispatched by mail, postage prepaid;
(ii) if by courier, when actually delivered by the courier company; or (iii)
if by facsimile with confirmed transmission, three (3) days after
transmission.
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be executed
by their duly authorized officers:
TEVA PHARMACEUTICAL INDUSTRIES LTD CEL-SCI CORPORATION
Signature: /s/ Roni Shiloh Signature: /s/ Geert R. Kersten
----------------------------- ---------------------
Name: Roni Shiloh, M.D. Name: Geert R. Kersten
----------------------------- ---------------------
Title: Medical Director Title: Chief Executive Officer
Signature: /s/ Coby Mazliah Signature:
----------------------------- ---------------------
Name: Coby Mazliah, Ph.D. Name:
----------------------------- ---------------------
Title: Director Clinical Trials Unit/
Teva/ Israel
Date: 2008 Date: 2008
---------- -----------
14
APPENDIX A
THE PROTOCOL
[See Attached]
TEVA PHARMACEUTICAL INDUSTRIES LTD CEL-SCI CORPORATION
Signature: /s/ Roni Shiloh Signature:
----------------------------- ---------------------
Name: Roni Shiloh, M.D. Name:
----------------------------- ---------------------
Title: Medical Director Title:
Signature: /s/ Coby Mazliah Signature:
----------------------------- ---------------------
Name: Coby Mazliah, Ph.D. Name:
----------------------------- ---------------------
Title: Director Clinical Trials Unit/
Teva/ Israel
Date: 2008 Date: 2008
---------- -----------
15
APPENDIX B
TRIAL ACTIVITIES
The following activities and costs:
>> Monitoring services, as needed in accordance with the Protocol on the
Commencement Date and for * patients
>> Payment to the physicians, the hospitals and testing laboratories
involved in the Trial and associated follow up, as long as such
payments are: (i) in the Territory (ii) in accordance with the
Protocol on the Commencement Date and (iii) for * patients
>> Clinical supply of the Drug, in an amount not exceeding the sum agreed
upon in the Distribution Agreement, for * patients, and for all other
study drugs in accordance with the requirements of the Protocol on the
Commencement Date
TEVA PHARMACEUTICAL INDUSTRIES LTD CEL-SCI CORPORATION
Signature: /s/ Roni Shiloh Signature:
----------------------------- ---------------------
Name: Roni Shiloh, M.D. Name:
----------------------------- ---------------------
Title: Medical Director Title:
Signature: /s/ Coby Mazliah Signature:
----------------------------- ---------------------
Name: Coby Mazliah, Ph.D. Name:
----------------------------- ---------------------
Title: Director Clinical Trials Unit/
Teva/ Israel
Date: 2008 Date: 2008
---------- -----------
16
APPENDIX C
THE PARTIES OBLIGATIONS
Roles and Responsibilities
TEVA and SPONSOR/Global CRO
-----------------------------------
Time Schedule
Study Code
SPONSOR
Global CRO
Contractor
Date
-----------------------------------
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Part 1
Time Schedule
----------------------------------------------------------------------------
Planning Phase
Final protocol
Clinical Phase
Patient recruitment time XXXXX
FPI XXXXX
LPI XXXXX
LPO XXXXX
Data Base Lock XXXXX
Complete Stat XXXXX
Clinical Study Report XXXXX
17
-----------------------------------
Roles & Responsibilities
Study Code
SPONSOR
Global CRO
Contractor
Date
-----------------------------------
------------------------------------------------------------------------------
Part 2
Roles and Responsibilities
------------------------------------------------------------------------------
If required, add and/or delete according to study specific requirements.
Tick relevant box SPONSOR and/or TEVA Site
*
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* * *
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*
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* * *
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18
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*
*
*
*
*
*
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*
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*
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* * * *
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* *
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* *
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* *
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* *
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* *
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19
-----------------------------------
*
*
*
*
*
*
-----------------------------------
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*
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*
------------------------------------------------------------------------------
TEVA PHARMACEUTICAL INDUSTRIES LTD CEL-SCI CORPORATION
Signature: /s/ Roni Shiloh Signature:
----------------------------- ---------------------
Name: Roni Shiloh, M.D. Name:
----------------------------- ---------------------
Title: Medical Director Title:
Signature: /s/ Coby Mazliah Signature:
----------------------------- ---------------------
Name: Coby Mazliah, Ph.D. Name:
----------------------------- ---------------------
Title: Director Clinical Trials Unit/
Teva/ Israel
Date: 2008 Date: 2008
---------- -----------
20
Appendix E
PHARMACOVIGILANCE AND RECALL AGREEMENT
This Pharmacovigilance and Recall Agreement (the "Agreement") is made as of
____________, 2008 by and between CEL-SCI CORPORATION, a corporation
incorporated under the laws of the State of Colorado, of 8229 Boone Boulevard,
Suite 802, Vienna, VA 22182, USA ("Supplier") and TEVA PHARMACEUTICAL INDUSTRIES
LTD, a limited liability company incorporated under the laws of Israel, of 5
Basel Street, Petah Tiqva 49131, Israel ("Teva").
1. Scope
This Agreement describes the procedures and defines the responsibilities of
Supplier and Teva to ensure adequate Adverse Event (AE) data exchange such that
regulatory reporting requirements can be met in a timely manner. This Agreement
replaces any previous safety information agreements between the companies on the
Product.
2. Definitions
Definitions used will conform to the current Volume 9A of the Notice to
Applicants: Volume 9A - Guidelines on Pharmacovigilance for Medicinal Products
for Human Use. Capitalized terms used in this Agreement and not defined herein
will have the meaning set forth in the Exclusive Distribution Agreement between
Supplier and Teva, dated ____________, 2008.
3. Global Safety Database
Supplier will maintain the global safety database for Post Marketing Spontaneous
Adverse Event (AE) reports related to the Product.
4. Case Exchange
Both parties are responsible for distribution of the safety information in their
own company safety network. The language of all exchanges will be English.
Abbreviations must be spelled out.
4.1. Spontaneous reports
Teva agrees to provide Supplier with all Adverse Event reports related to
Product. The format is not necessarily that of CIOMS I but should contain all
data elements to be able to generate a CIOMS I report. Source documents should
remain locally for inspection purposes and should be provided on request. Case
exchange is preferably done by email
Each party agrees to provide the other party with copies of all Adverse Events
reports within 3 business days of submission.
Both parties agree to answer in a reasonably exhaustive manner all questions
that the other party might raise that affect case evaluation or regulatory
reporting with regard to exchanged cases.
The date of receipt by the original recipient of any Adverse Event report must
be recorded on each report exchanged.
2
4.2. Follow up information
The party notified first on an adverse reaction is responsible for obtaining
follow-up information required for proper assessment of the case. Questions
regarding a specific case must be communicated to the initial party to request
the information from the reporter. Follow-up data will be exchanged in the same
manner as initial data, within the same timeframes. If site visits are
requested, representatives from both parties will be allowed to participate.
4.3. Reports from literature
Supplier will have the primary responsibility for reviewing the literature
outside the Territory. Reports of serious published ADRs will be provided as
described above. Teva will be primarily responsible for checking the literature
published in the Territory and sending cases to Supplier.
4.4. Reports on overdose, abuse and misuse, lack of efficacy, transmission of
infectious agents, medication errors.
Reports on overdose, abuse and misuse as well as lack of efficacy should be
reported to Supplier according to the timelines as mentioned in Clause 4.1
above. Any suspected transmission of a infectious agent via a medicinal product
is also considered an adverse event as referred to in Clause 4.1. Cases of
medication errors which are associated with adverse events should also be
reported as referred to in Clause 4.1.
4.5. Reports from outcomes of use in pregnancy and lactation
All reports from health care professionals relating to pregnancies where the
foetus may have been exposed should be followed up and reported to Supplier
according to Clause 4.1. For reports from consumers reasonable attempts should
be made to follow up with the physician.
5. Causality assessment
Generally the reporter's causality assessment will be accepted. Supplier and
Teva may however express another opinion. The most conservative opinion will
determine further reporting.
6. Expedited Reporting
Supplier is responsible for determining seriousness, expectedness per the
package insert and the company's opinion of relatedness. Supplier is responsible
for preparing any regulatory forms for submission in the Territory.
Teva will make the determination as to whether a report meets criteria for
expedited reporting to regulatory authorities in the Territory.
Teva will be responsible for submission of expedited reports to the regulatory
authorities in the Territory.
Both parties will submit the appropriate reports of individual case reports to
the regulatory authorities of the countries in their territories within the time
frames required by the current legislation in each ountry.
3
7. Periodic Reporting
Supplier will be responsible for preparing and reporting of Periodic Safety
Update Reports (PSUR) according to the current guidelines. The PSUR will be
forwarded to Teva for submission to local authorities in the Territory.
8. Regulatory requests for additional information
8.1. Additional information on a specific case
The party who received the regulatory authority request for follow-up
information will submit the response to the requesting regulatory authority. If
necessary, the party who first received the case report will obtain the
requested information from the reporter.
8.2. Additional information of a more general nature
Regulatory authority requests for safety information of a more general nature
will be answered by the party who received the initial request. Teva will
provide to the supplier a copy of the regulatory agency's request for general
information and their proposed response to the request prior to its submission
for review and comment.
9. Compliance
Teva is responsible for ensuring that local Pharmacovigilance and drug safety
regulatory requirements are met in the Territory. Without limiting the
foregoing, Teva will comply with local regulation's with all regulations and
laws applicable to the Territory.
10. Signals/Actions
Each company will notify the other company as soon as possible of any regulatory
actions or pending actions that might result in: (i) a change in labeling or
market restriction, (ii) market authorization withdrawal or suspension, or (iii)
change of local labeling which is thought to be important from a safety view
point; in each case, to the extent such action is suggested by signals detected
by the pharmacovigilance program, issue evaluation, liaison with regulatory
authorities, or new requirements defined by the regulatory authorities.
11. Teva's response time to reports on Adverse Events:
Adverse Event (AE): within 5 days from awareness of the event to Teva or any
of its subsidiaries or other license partners involved in marketing of the
Product.
Serious Adverse Events (SAE): within 24 hours from awareness of the event for
SAE resulting in death or life threatening events, and within 48 hours for
all other SAE.
12. Contacts
It is the responsibility of each company to notify the other company in writing
of any changes to the contact information as soon as possible.
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For CEL-SCI, all correspondence about this agreement should be sent to:
Name: John Cipriano
Address: CEL-SCI Corporation,
8229 Boone Boulevard, Suite 802
Vienna, VA, 22182 USA
Tel: (703) 506-9460
Fax: (703) 506-9471
Email: *
For CEL-SCI, all Adverse Event reports should be sent to:
Name: John Cipriano
Address: CEL-SCI Corporation
8229 Boone Boulevard, Suite 802
Vienna, VA, 22182 USA
Tel: (703)-606-9460
Fax: (703) 506-9471
Email: *
For Teva, all correspondence about this agreement should be sent to:
Name: Shelly Lavy
Address: Teva Israel, P.O.Box 8077 Netanya 42504, Israel
Tel: *
Fax: *
Email: *
For Teva, all Adverse Event reports should be sent to:
Name: Shelly Lavy
Address: Teva Israel, P.O.Box 8077 Netanya 42504, Israel
Tel: *
Fax: *
Email: *
13. Recalls
Teva and the Supplier shall comply with local regulations in the Territory
regarding any case necessitating a recall of the Product from the market. In the
event that a recall of the Product in the Territory is being contemplated for
any reason, each party shall promptly consult with the other with the view to
deciding the appropriate action to take with respect thereto.
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In any event, the final decision on a recall will comply with any resolution
issued by the regulatory authorities for each affected Country in the Territory
concerning the specific case in which a recall of the Product is being
contemplated.
In the event a recall is due to the negligence or improper action of Teva, Teva
shall bear the costs related to the recall. In any other event, Supplier shall
bear the cost related to the recall.
14. Term
The term of this Agreement will commence upon signature hereof by both parties
and will continue until expiration or termination of the Exclusive Distribution
Agreement between Supplier and Teva, dated ____________, 2008 (including the
expiration of any wind-down period related to the sale of Products, as described
therein).
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CEL-SCI CORPORATION TEVA PHARMACEUTICAL INDUSTRIES LTD
Signature: /s/ Geert R. Kersten Signature: /s/ Judith Vardi
----------------------------- ---------------------
Name: Geert R. Kersten Name: Judith Vardi
----------------------------- ---------------------
Title: Chief Executive Officer Title: V.P.IMAT
----------------------------- ---------------------
Date: August 18, 2008 Date: August 18, 2008
----------------------------- ---------------------
Signature: /s/ Efrat Klachevsky
---------------------
Name: Efrat Klachevsky
-----------------------------
Title: Direct, Business Developement
Date: 07/08/08
------------------------
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