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EXHIBIT 10.30
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
AGREEMENT
This Agreement is made as of September 29, 1997 between Xxxxx Medical
Limited whose head office is situated at Xxxxx House, Regent Park, Xxxxxxxx
Xxxx, Xxxxxxxxxxx, Xxxxxx XX00 0XX, Xxxxxx Xxxxxxx (hereinafter referred to as
"Xxxxx") and OraVax, Inc., a Delaware corporation, 00 Xxxxxx Xxxxxx, Xxxxxxxxx,
Xxxxxxxxxxxxx, 00000, X.X.X. (hereinafter referred to as "OraVax").
WHEREAS:
X. Xxxxx is engaged in the development, manufacture, marketing and sale
of a vaccine against yellow fever ("YF");
X. Xxxxx seeks assistance in the conduct and monitoring of Phase III
Clinical Trials (as such term is defined in Section 1.1) in the United States;
X. Xxxxx seeks a collaboration with a reputable and experienced vaccine
company in the United States to market the Product (as such term is defined in
Section 1.1) in the United States;
D. OraVax is an experienced participant in the pharmaceutical and
vaccine business in the United States, with special expertise concerning YF
vaccines;
X. Xxxxx and OraVax have conducted market research in the United States
which indicates that there is a substantial and potentially profitable market
for an effective YF vaccine product;
X. Xxxxx and OraVax each wish to participate in certain clinical
studies, the regulatory approval, marketing and distribution of the Product as
described herein and in return to receive benefits arising from the commercial
exploitation of such Product in the Product Territory (as such term is defined
in Section 1.1).
WITNESSETH
NOW, THEREFORE, in consideration of the mutual covenants herein and for
other good and valuable consideration, the receipt and sufficiency of which are
hereby acknowledged, Xxxxx and OraVax hereby agree as follows:
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SECTION 1. DEFINITIONS AND INTERPRETATION
1.1 When used in this Agreement, the following terms shall have the
following meanings:
(a) "Additional Periods" shall be as defined in Section 3.3.
(b) "Budgets" shall mean the agreed budgets for clinical
trials and/or promotional activities as described in Sections 2.4 and 3.10,
respectively.
(c) "cGCP Regulations" shall mean regulations set forth in
Parts 50 and 56 of Volume 21 of the U.S. Code of Federal Regulations pertaining
to ethical and scientific quality standards for designing, conducting, recording
and reporting clinical trials that involve the participation of human subjects.
(d) "Confidential Information" shall be as defined in Section
9.2.
(e) "Damages" shall mean all actions, claims, demands, losses,
damages, costs and expenses whatsoever, wheresoever and howsoever arising.
(f) "Xxxxx" shall be as defined in the first paragraph of this
Agreement.
(g) "FDA" shall mean the United States Food and Drug
Administration or any successor thereof.
(h) "GM" shall mean the gross margin from sales of the Product
in the Product Territory calculated as per the example in Section 5.2.
(i) "GM Target" shall mean the minimum GM mutually agreed upon
by the Parties from time to time. The GM Target shall initially be mutually
agreed upon by the Parties at least six months prior to the anticipated date of
Product Approval.
(j) "ICH" shall mean the International Conference on
Harmonisation.
(k) "IND" shall mean Investigational New Drug application.
(l) "Initial Period" shall be as defined in Section 3.2.
(m) "OraVax" shall be as defined in the first paragraph of
this Agreement.
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(n) "Parties" shall mean Xxxxx and OraVax.
(o) "Phase III Clinical Trials" shall mean all clinical trials
conducted in support of Product Approval and prior to the date of approval of
the PLA by FDA. Unless specifically otherwise stated, all references in this
Agreement to trials, clinical trials and vaccine trials shall be deemed to be
references to Phase III Clinical Trials.
(p) "Phase IV Clinical Trials" shall mean clinical trials
conducted with approved Product subsequent to first grant of Product Approval.
(q) "PLA" shall mean U.S. Product License Application relating
to the Product.
(r) "Product" shall mean Xxxxx'x XX 17D vaccine product
manufactured to comply with the specifications approved by the Medicines Control
Agency in the United Kingdom and described in Xxxxx'x current data sheet
supplied with its YF 17D vaccine in the United Kingdom and any improvements
thereon.
(s) "Product Approval" shall mean approval of the PLA and
issuance of a product license for Product by the FDA.
(t) "Product Territory" shall mean the United States.
(u) "Trademarks" shall be as defined in Section 8.1.
(v) "YF" shall be as defined in Recital A to this Agreement.
1.2 In the interpretation of this Agreement unless inconsistent with
the context or the subject matter:
(a) References to the singular shall include references to the
plural and vice versa;
(b) References to clauses and Schedules are references to
clauses and Schedules of this Agreement;
(c) References to persons shall include references to all
legal entities including but not limited to bodies corporate and vice versa;
(d) Words denoting any gender shall include all genders;
(e) Clause headings shall in every case be disregarded.
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SECTION 2. CLINICAL TRIALS, PRODUCT DEVELOPMENT
AND COMPLIANCE WITH LAWS AND REGULATIONS
2.1 Application for PLA by Xxxxx.
(a) The Parties shall cooperate and work in good faith to
obtain Product Approval in the Product Territory. OraVax and Xxxxx shall, in
accordance with this Agreement, provide such assistance to one another as both
Parties agree is reasonable and necessary to obtain Product Approval. It is the
intention of the Parties that OraVax shall be permitted to accompany Xxxxx to
all meetings with the FDA concerning Product Approval in the Product Territory.
Xxxxx shall supply OraVax with copies of all information that may be relevant to
obtaining Product Approval and all written documentation submitted by Xxxxx to
the FDA concerning the Product Approval, as well as permission to cross file
against existing submissions of Xxxxx to the FDA, as necessary to file a U.S.
IND for the Product.
(b) OraVax acknowledges that Xxxxx will be the holder and sole
legal and beneficial owner of the PLA and all documents used to support the PLA.
Notwithstanding any other provision set forth in this Agreement, access of
OraVax to a PLA shall at all times be subject to the discretion of Xxxxx and in
any event only for the strict purposes of this Agreement.
(c) OraVax acknowledges that at all times Xxxxx shall remain
the owner and manufacturer of the Product and shall be so identified on labels,
package literature and other marketing materials in the format requested by
Xxxxx, subject to FDA requirements.
(d) OraVax acknowledges that, except for the specific
distribution rights granted in this Agreement, OraVax will not acquire any
rights, including but not limited to intellectual property rights, in or in
relation to the Product or Xxxxx'x business.
2.2 Conduct of Clinical Trials by OraVax. OraVax agrees to assist in
conduct of clinical trials relating to Product Approval in the Product
Territory. OraVax and Xxxxx shall mutually agree on the objective and design of
clinical trials, and shall review and agree on proposals, case report forms,
consent forms, and the statistical analysis plan. OraVax shall be responsible
for the selection of clinical investigators (which investigators shall be
suitably qualified and able to conduct the clinical trials in accordance with
the protocol agreed upon by OraVax and Xxxxx); negotiation of clinical trials
agreements and payments to investigators; implementation and clinical monitoring
of the trials; preparation and distribution of study documents, including
complete clinical trials binders; adverse event reporting; collection, storage
and shipment of serum specimens to Xxxxx for serological testing;
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Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
and analysis of data. Unless otherwise requested by Xxxxx, OraVax and Xxxxx
shall jointly prepare all clinical trial reports, including reports to the FDA;
provided, however, that final approval of such reports shall in all cases be
made by Xxxxx. OraVax shall prepare and maintain study specific SOPs as needed,
and will ensure the complete documentation of the trials. OraVax shall ensure
that trials are conducted in accordance with cGCP Regulations, the tripartite
harmonised guidelines issued by the ICH and the Declaration of Helsinki, and
meet all necessary standards required in support of the PLA. OraVax shall
maintain in force clinical trials insurance adequate to cover estimated
liability that may arise in relation to these trials, the amount of which shall
be mutually agreed upon by OraVax and Xxxxx; provided, however, that in no event
shall OraVax maintain clinical trials insurance in an amount less than [**].
2.3 Reports and Data from Clinical Trials. OraVax agrees to provide
Xxxxx with data and reports when generated from all clinical trials and in a
timely manner. OraVax and Xxxxx shall discuss and agree on procedures for data
handling and analyses required in support of IND and PLA filings.
2.4 Payment for OraVax Costs. OraVax and Xxxxx will discuss in good
faith all actions related to clinical trials and shall agree in advance on the
Budgets for the trials; provided, however, that Xxxxx shall have the right to
final approval of the Budgets. As will be provided specifically in the Budgets,
Xxxxx shall pay OraVax for salary and reasonable and customary indirect costs of
such OraVax staff as the Parties shall have mutually agreed to be reasonably
necessary to be deployed to support the agreed-upon clinical trials. To the
extent that the following may be specified in the Budget, or as otherwise agreed
by Xxxxx in writing, Xxxxx shall pay all necessary and reasonable external costs
of the trials, including payments to clinical investigators, overhead charges to
investigator institutions, specimen handling and shipping costs, statistical
services, monitoring services and travel, safety laboratory tests, and other
out-of-pocket costs incurred by OraVax or its contractors. In the event that
OraVax and Xxxxx fail to agree on the Budgets, this Agreement shall terminate in
accordance with Section 14.1(c), and each Party shall not incur any costs for
the account of the other during the given notice period.
2.5 Supply and Materials for Clinical Trials. Xxxxx agrees to provide
OraVax with the supplies of Product, including diluent, reasonably necessary to
conduct clinical trials in accordance with the agreed upon protocol, at no cost
to OraVax. As required by trial design, Xxxxx will supply placebo vaccine and
will randomize and appropriately label active and placebo vaccine to be used in
double-bind trials, at no cost to OraVax. Xxxxx will provide to OraVax a
description of the
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vaccine and/or technical documentation necessary for OraVax to prepare an
investigator's brochure for distribution in advance of vaccine trials. It is
hereby agreed that the information to be provided by Xxxxx may be in the form of
package inserts supplied with approved Product in the U.K.
2.6 Neutralization Tests. Xxxxx will perform neutralization tests and
any other special serological studies on samples collected during the clinical
trial. If Xxxxx is unable to conduct these tests, OraVax or a third party may
perform them, as mutually agreed by both Parties. Xxxxx shall pay the previously
agreed cost associated with the performance of these tests.
2.7 Phase IV Clinical Trials. OraVax and Xxxxx acknowledge that it
may be desirable to conduct certain Phase IV Clinical Trials in the Product
Territory. The Parties agree to discuss opportunities for increasing market
share by such additional clinical trials aimed at broadening clinical
indications and demonstrating safety in subgroups requiring the vaccine (e.g.
HIV-infected subjects). Any such Phase IV Clinical Trials in the Product
Territory shall be conducted in a collaborative manner.
2.8 Non-Solicitation. Unless otherwise agreed, the Parties shall not
solicit the employment of any person who at the time of such solicitation is an
employee of the other.
SECTION 3. MARKETING AND DISTRIBUTION
3.1 Appointment as Distributor. Xxxxx hereby appoints OraVax, and
OraVax hereby agrees to act as the exclusive marketer and distributor to
civilian and military markets in the Product Territory of the Product and OraVax
hereby agrees to act in that capacity subject to the terms and conditions of
this Agreement.
3.2 Term. The initial term of OraVax's appointment under this
Agreement shall commence on the date of this Agreement and end five years after
the date of grant of the Product Approval for the Product (the "Initial
Period").
3.3 Renewals. This Agreement shall continue to be automatically
renewed for successive periods of two (2) years after the Initial Period (the
"Additional Periods") unless terminated in accordance with Section 14.
3.4 Identification of OraVax as Distributor. OraVax shall be
acknowledged as the distributor of the Product on labels, package literature and
other marketing materials prepared for the Product Territory in a format
acceptable to and required by the FDA, and to be mutually agreed upon by OraVax
and Xxxxx. The Parties agree that an unintentional failure by either Party to
comply with this Section 3.4 shall not constitute grounds for termination of
this Agreement under Section 14.
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3.5 Exclusive Appointment. Xxxxx agrees not to appoint any other
person to act as its distributor for the Product in the Product Territory during
the currency of this Agreement except that for transitional purposes Xxxxx may,
during the period of six months expiring with the termination hereof, appoint
OraVax's successor (if any) and allow such successor to make himself known as
Xxxxx'x distributor able to do business from a specified date being the day
after the termination hereof.
3.6 No Sales in the Territory by Xxxxx. For the duration of OraVax's
exclusive rights in the Product Territory granted hereunder, Xxxxx will not
undertake to sell the Product to any person, company or firm for resale in the
Product Territory and not to sell the Product to any person, company or firm
residing or trading outside the Product Territory which Xxxxx has reasonable
grounds to believe is purchasing the Product for the purpose of re-selling the
Product in the Product Territory.
3.7 No Sales outside the Territory by OraVax. OraVax shall not sell
the Product outside the Product Territory or sell the Product to a third party
within the Product Territory where there are reasonable grounds for OraVax to
believe that the third party may, whether directly or indirectly, sell or cause
to be sold the Product outside the Product Territory.
3.8 Expansion of Product Territory.
(a) OraVax may identify opportunities for expansion of
sales of the Product outside the Product Territory, other than in markets
already served by Xxxxx, its affiliates or preexisting licensees. OraVax shall
inform Xxxxx of any such opportunity and of its wish to pursue such opportunity.
Xxxxx shall notify OraVax whether or not the territory in question is available
to OraVax with regard to distribution of the Product and in the event that Xxxxx
notifies OraVax that such territory is so available Xxxxx shall afford to OraVax
for a period of 60 days after such notification by Xxxxx a right of first
negotiation with respect to entering into arrangements for distribution of the
Product in any such new territory. In the event that Xxxxx agrees to OraVax
pursuing any such opportunity, OraVax shall inform Xxxxx on a timely basis of
all subsequent discussions regarding such market expansion. Xxxxx shall have the
final right to approve the terms of such expansion of the Product Territory
covered by this Agreement. It is the intention of the Parties to expand the
market for the Product to as many countries outside the U.S. as possible. Upon
expiration of such 60-day period, or upon earlier notice from OraVax that OraVax
does not wish to negotiate for the right to distribute the Product in the
specified expanded market, Xxxxx shall be free to negotiate with third parties
concerning distribution in such market.
(b) Specifically with regard to the expansion of the
Product Territory under this Section 3.8, OraVax is not an agent for Xxxxx and
is not authorized to and
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shall not enter into any negotiation on behalf of Xxxxx and therefore shall not
represent to any party that it is employed by or acting on behalf of Xxxxx in
any capacity and further agrees that Xxxxx shall have no obligation to OraVax to
enter into any transaction (no matter how far negotiations have proceeded with
respect to the transaction) and in doing so incur no obligation to OraVax or any
third party.
(c) This Section 3.8 shall not apply if OraVax introduces
to Xxxxx a party with whom Xxxxx or any of its affiliates has already been in
contact regarding distribution of the Product or if Xxxxx or any of its
affiliates has not been in contact but knew of the existence either from that
party directly or from another intermediary.
3.9 OraVax's Status as Independent Contractor. The relationship
between the Parties is that of seller and buyer and shall not be deemed to be
that of principal/agent, joint venture, partnership or otherwise. Otherwise than
as expressly permitted by this Agreement, OraVax is not authorized to act on
behalf of Xxxxx and shall not act or purport to act to obligate or bind Xxxxx or
hold itself out as entitled to obligate or bind Xxxxx in any way without the
express written consent of Xxxxx, but shall act as an independent contractor
buying for itself and selling in its own name and at its own risk subject only
to Section 13.1.
3.10 Promotional Efforts of OraVax. OraVax shall exercise its best
efforts to promote, extend and increase market share of the Product in the
Territory, including negotiations with the U.S. Armed Forces in order to obtain
the military market, and promotion of the Product at major consumer group
meetings, including the American Society of Tropical Medicine & Hygiene and the
Travel Medicine Society. Subject to Budget approval by the Parties, OraVax and
Xxxxx shall share equally the costs for such exceptional promotional activities.
3.11 Promotional Material. Xxxxx shall supply to OraVax at no cost
one copy of any marketing materials used by Xxxxx in relation to the Product and
that may be used by OraVax in the production of marketing materials within the
Product Territory. OraVax shall be permitted to make additional copies of such
marketing materials at its expense. OraVax agrees not to use any sales aids or
promotional materials that have not been supplied or approved by Xxxxx. OraVax
shall be responsible for filing copies of all promotional materials with the FDA
in accordance with applicable FDA regulations, and for ensuring that such
materials comply with applicable FDA regulations.
3.12 Sales Targets. OraVax shall use its best efforts to meet the
minimum sales targets set forth on Schedule 3 to this Agreement, as such
Schedule 3 may be amended from time to time with the written agreement of the
Parties. The Parties agree to review sales targets within six months following
Product Approval and on an annual basis thereafter.
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Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
3.13 OraVax's Conduct. OraVax shall not:
(a) pledge the credit of Xxxxx or affiliates of Xxxxx in
any way;
(b) engage in any conduct which in the opinion of Xxxxx is
prejudicial to Xxxxx'x business or the marketing of the Product; or
(c) be concerned or interested in the development,
manufacture, sale, promotion, marketing or importation into the Product
Territory of any goods which may compete directly or indirectly with sales of
the Product.
3.14 Obligations of Xxxxx. Xxxxx shall not be under any obligation to
manufacture or to continue the manufacture of the Product and may at any time
make such alterations to the Product's specifications as it thinks fit or as are
required by the FDA or other applicable regulatory authority including changes
in the design, production or packaging or by the withdrawal of the Product.
3.15 Packaging of the Product.
(a) Xxxxx will supply the Product in packed form as agreed
by the Parties at the time of placing an order and approved by the FDA.
(b) The Product will be supplied in Xxxxx packaging,
subject to the provisions of Section 3.4. The packaging and all package inserts
will be in the English language. OraVax shall be responsible for ensuring that
the specifications for packaging and packaging inserts comply with the
requirements of the FDA. Any subsequent modification required by the FDA shall
be made known to Xxxxx in writing by OraVax within ten (10) days of the time
which OraVax first becomes aware of it. The packaging shall include, in a form
acceptable to Xxxxx, an acknowledgment that the Product is manufactured by Xxxxx
and that the Trademarks are registered trademarks of Xxxxx.
SECTION 4. SUPPLY OF PRODUCT
4.1 Forecasts of Product Requirements. At least [**] prior to the
expected date of the first Product Approval, OraVax shall provide to Xxxxx
(separately for civilian and military markets) a written forecast by calendar
quarter (or part thereof as the case may be) of its expected requirement of
Product for the period of twelve months immediately following the grant of
Product Approval. Such forecast shall be
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Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
updated within ten days of commencement of each calendar quarter. Xxxxx shall
indicate in writing whether it accepts each such forecast and upon written
acceptance by Xxxxx of each forecast the amount of Product specified in relation
to the fourth calendar quarter of each such forecast shall constitute and be
deemed by the Parties a binding order for Product to be supplied by Xxxxx to
OraVax on the terms of this Agreement (a "Binding Order") provided that in
respect of each Binding Order the amount of Product specified shall be within
the range plus or minus [**] of the amount of Product first accepted by Xxxxx in
relation to the calendar quarter in question.
4.2 Orders. OraVax shall submit written orders for supply of Product
at least twelve weeks prior to the date that it requires delivery of Product by
Xxxxx each such actual order shall be for a reasonable quantity of Product and
in any event the amount of Product ordered by OraVax shall be in accordance with
the Binding Orders accepted by the Parties pursuant to Section 4.1 above.
4.3 Binding Effect of Orders. Orders from OraVax shall be binding on
the Parties upon written acceptance by Xxxxx.
4.4 Supply. Xxxxx shall use its reasonable commercial efforts to
supply the Products in accordance with such Binding Orders.
4.5 Stocks of the Product. Xxxxx shall maintain stocks of the Product
consistent with OraVax's sales forecasts. OraVax shall maintain stocks to supply
the Product sufficient to meet customer demand under normal market conditions,
such quantities to be defined by the Parties and reviewed periodically. In the
event of an emergency, such as a YF epidemic in the Product Territory or actual
orders from OraVax in excess of the Binding Order quantities, Xxxxx shall
exercise reasonable efforts to supply the Product in quantity sufficient to meet
increased demand but always subject to Xxxxx'x previous commitments and to the
availability of sufficient stock of the Product on short notice.
4.6 Marketing Plans. A strategy for promoting the Product and for
increasing market share will be developed between both Parties and carried out
by OraVax. OraVax shall prepare a marketing plan for each calendar year and will
submit such plans to Xxxxx for review at least 90 days before the commencement
of each calendar year. The marketing plan shall include priorities for promoting
the Product, sales forecasts and product positioning and such other information
as the Parties shall reasonably require.
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Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
SECTION 5. PRICE AND PAYMENT
5.1 Share of Gross Margin. Xxxxx and OraVax agree to share the GM
[**] except in the case that the GM achieved on sales of Product is less than
the GM Target in force at the date payment is due from OraVax to Xxxxx in which
case OraVax shall retain [**] of the GM calculated in accordance with Section
5.2 and the balance shall be remitted to Xxxxx provided that the amount remitted
to Xxxxx shall in no event be less than Xxxxx Cost of Production at the time
payment is due, plus [**] of Xxxxx Cost of Production. Xxxxx shall invoice
OraVax for Product ordered by OraVax in accordance with Section 4.3 at the time
of shipment by Xxxxx at prices that provide for reimbursement of Xxxxx Cost of
Production, being the cost of manufacturing, packaging, release testing,
delivery, insurance, freight, taxes, and duties plus a further [**] of such Cost
of Production. OraVax Cost of Sales shall be cost of handling and shipping
Product to its customers and any taxes, duties or tariffs paid by OraVax in
respect of the Product.
5.2 Calculation of Gross Margin. The following is an example of a
calculation of the sharing of GM under this Agreement (numbers are not actuals):
Gross sales price received by OraVax $ 1.00
Deduct: - [**]
Gross Margin [**]
Amount payable to Xxxxx by
OraVax [**] [**]
5.3 Audit and Inspection. OraVax shall maintain complete sales
documentation, and Xxxxx shall maintain complete production documentation. Each
Party shall have a right to audit and take copies of sales or production
documentation (as the case may be) of the other Party to verify correctness of
Cost of Production, Cost of Sales or GM, as the case may be, and to inspect
storage facilities used by the other Party in connection with storage and
handling of the Product; provided that audits contemplated by this Section 5.3
shall be conducted no more than once per year per Party by an independent third
party and at the cost of the Party conducting the audit unless a material
difference in the Cost of Production, Cost of Sales or GM is found, in which
case the Party subject to the audit shall forthwith pay to the other Party the
amounts found to be due and shall further bear the reasonable costs of the
audit.
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5.4 Payment for Product Shipped. On the last day of each month,
OraVax shall make a single payment by wire transfer to Xxxxx. This payment shall
include Xxxxx'x share of the GM on sales of Product for which OraVax was due to
be paid by its customers during the immediately preceding month without regard
to whether or when OraVax is paid by customers (for example, amounts due to
Xxxxx that relate to customer payments due to OraVax on June 3 and June 29 shall
be paid by OraVax to Xxxxx on July 31, even if OraVax did not in fact receive
such customer payments on their respective due dates), and payment of invoices
received from Xxxxx pursuant to Section 5.1 in the preceding month. OraVax shall
provide with each payment a statement including the Xxxxx invoice numbers and
amounts and details of the calculation of GM.
5.5 Payment in U.S. Dollars. All payments required to be made
pursuant to this Agreement shall be made in United States Dollars unless
otherwise agreed in writing between the Parties
SECTION 6. PACKING, DELIVERY AND RISK IN TRANSIT
6.1 Xxxxx will pack the Product suitable for delivery and deliver
each shipment of Product to the Premises in the Product Territory as shall be
designated by OraVax and agreed by Xxxxx. Xxxxx shall invoice Product F.O.B.
OraVax's Cambridge, Massachusetts premises (the "Premises").
6.2 Acceptance of, and risk in, the Product by OraVax shall be deemed
to have taken place upon delivery of a packed consignment to the Premises.
Notwithstanding the foregoing, Xxxxx shall retain title to the Product until
Xxxxx has received payment in full in respect thereof. If an event described in
Section 14.1(b)(i) or (ii) occurs with respect to OraVax, Xxxxx shall have the
right to (i) repossess Product for which Xxxxx has not received payment in full,
and (ii) enter into any premises owned or controlled by OraVax at which Product
is stored for such purpose.
SECTION 7. QUALITY CONTROL
7.1 Storage and Shipment Specifications. Xxxxx shall provide to
OraVax detailed specifications for storage and shipment of the Product. OraVax
agrees to comply with such specifications. Xxxxx will be paid by OraVax for any
Product damaged subsequent to receipt by OraVax.
7.2 Rotation of Stocks. OraVax shall monitor expiration dates and
ensure proper rotation of stocks.
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7.3 Replacement of Defective Product. OraVax shall inspect all
batches of Product received. In the event that a batch is found to be damaged or
not in good order, OraVax shall so notify Xxxxx within 30 days' of delivery of
such batch and Xxxxx shall promptly replace the notified Product or allow a full
credit, the specific remedy in such case to be determined solely by Xxxxx. If
Xxxxx subsequently determines that such Product is not damaged or such damage is
the fault of OraVax, OraVax shall be liable to make payment in full in respect
of both the purportedly damaged Product and any replacement Product delivered by
Xxxxx.
7.4 Release Testing. Xxxxx shall be responsible for release testing
in the country of manufacture prior to packaging of the Product. OraVax shall be
responsible for obtaining a certificate of approval from CBER and any other
release testing or procedure in the Product Territory.
7.5 Product Defects.
(a) OraVax shall give immediate written notice to Xxxxx of
any alleged manufacturing or other defect in the Product of which OraVax becomes
aware and of any possible expense, liability, cost, claim or proceedings arising
from the alleged defect.
(b) With respect to any adverse drug experiences alleged to
be caused by and any alleged manufacturing or other defect in the Product,
OraVax shall not take any action or make any admission of liability or other
disclosure that is not required by law to any third party with respect to
claims, either in the name of OraVax or on behalf of Xxxxx without Xxxxx'x prior
written consent.
7.6 Return Policy. No returns shall be accepted unless mutually
agreed upon by the Parties. In the event Product is returned in accordance with
this Section 7.6, the cost of such returned Product shall not be passed to or
accepted by Xxxxx without the prior consent of Xxxxx.
7.7 Compliance with Regulation. OraVax shall distribute the Product
to consumers in full compliance with local and national regulations for the
distribution of yellow fever vaccines. The Product shall be distributed only to
vaccinating centers approved and designated by State and Health Departments in
the U.S., or to the U.S. military and other U.S. government purchasers.
7.8 Consultation to Consumers. OraVax shall provide expert advice and
consultation to consumers on the Product and its utilization. Such advice and
consultation may refer to the Product itself or to the general use of YF
vaccines for international travel. In no event shall OraVax give any warranties
in relation to the Product other than those printed on packaging of the Product
or agreed upon mutually. Any additional warranties must be agreed upon by the
Parties in writing.
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SECTION 8. INTELLECTUAL PROPERTY RIGHTS
8.1. Rights of Xxxxx to Intellectual Property. OraVax recognizes that
all intellectual property rights covering or relating to the Product including
but not limited to all patents and patent applications in respect of the
Product, technical information and other know how, all trademarks of Xxxxx used
on or relative to the Product (hereinafter referred to as "Trademarks"), all
registered and unregistered design rights in respect of the Product and
copyrights in all labels and marks attached to the Products and packages,
leaflets and brochures and all clinical trial data and promotional and
advertising literature supplied by Xxxxx or on behalf of Xxxxx or generated by
OraVax in respect of the Product, are the exclusive property of Xxxxx.
8.2 Trademark Registrations. Xxxxx shall make any applications for
registration of the Trademarks in the Product Territory in its own name. Should
it be desirable in the opinion of Xxxxx for an application to be made for the
registration in the Product Territory of any of the Trademarks, OraVax shall
render all reasonable assistance to Xxxxx in connection therewith. Should it be
desirable in the opinion of Xxxxx that any such application should be made in
the name of OraVax such application shall be made by OraVax at the expense of
Xxxxx; and any registration so obtained shall be promptly assigned to Xxxxx or
its nominee on request or upon termination of this Agreement.
8.3 License of Trademark to OraVax. Should it be desirable in the
opinion of Xxxxx, Xxxxx shall xxxxx OraVax a license to use the Trademarks which
are registered in the Product Territory. Any such grant shall be at the cost of
Xxxxx. Upon the termination (as the case may be) of this Agreement, Xxxxx shall
be entitled at its cost to take all steps necessary to terminate any license
granted to OraVax under this Section 8.3 and OraVax shall:
(a) Cooperate with Xxxxx as and when requested by Xxxxx in
having any such license so terminated; and
(b) Not oppose or hinder Xxxxx in taking any such steps to
have any such license so terminated.
Other than as is necessary for the proper performance of this
Agreement by OraVax, no license, express or implied, is granted by this
Agreement by Xxxxx under any of the Trademarks or those of affiliates of Xxxxx.
8.4 Prior Xxxxx Approval of Trademark Use. Any proposed use of the
Trademarks by OraVax shall be submitted to Xxxxx for its prior written approval
and
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15
the Trademarks shall only be used by OraVax in the manner and form so approved
by Xxxxx.
8.5 Use of Trademarks. OraVax shall use its best endeavors to
preserve the value and validity of the Trademarks and, in particular, OraVax
will ensure that the Trademarks are always fully capitalized or given other
distinctive typographic treatment, and a reference (whether by reference from
the first use of the Trademarks to footnotes or otherwise) will indicate that
the Trademarks are the trademarks or the registered trademarks, as the case may
be, of Xxxxx.
8.6 OraVax Logo. OraVax shall be entitled to use its corporate logo
on any labeling of the Product provided that OraVax's corporate logo is in a
form, position and size previously agreed to in writing by Xxxxx. Xxxxx
undertakes not to appropriate in any way any of OraVax's intellectual property
rights covering or relating to OraVax's logo. OraVax undertakes not to
appropriate in any way any of Evan's intellectual property rights covering or
relating to Evan's logo. OraVax shall not use in its business any trademarks
which are similar or substantially similar to or so nearly resemble the
Trademarks so as to be likely to cause deception or confusion.
8.7 Infringement. OraVax shall promptly notify Xxxxx of any actual,
threatened or suspected infringement in the Product Territory of any Trademarks
which comes to OraVax's notice, and of any claim by any third party so coming to
its notice that the importation of the Product into the Product Territory, or
its sale therein infringes any rights of any other person, and OraVax shall at
the request and expense of Xxxxx do all such things as may be reasonably
required to assist Xxxxx in taking all proceedings in relation to any such
infringement or claim.
SECTION 9. CONFIDENTIALITY
9.1 Mutual Confidentiality Covenant. Each Party shall keep secret and
confidential all Confidential Information of the other (as defined below)
disclosed, made available or acquired for the purposes of this Agreement. Each
Party shall also use its best endeavors to prevent the disclosure to any person,
other than its employees and authorized agents (and then only when such
disclosure is required for the proper performance of this Agreement), of all
Confidential Information of the other. Each Party shall use its best endeavors
to ensure that the Confidential Information of the other is not used except as
expressly allowed by this Agreement. Each Party shall be responsible for
ensuring that its employees and authorized agents do not disclose Confidential
Information of the other to a third party or make any unauthorized use of the
Confidential Information. Each Party shall be responsible for maintaining the
Confidential Information with the same degree of care which it uses to maintain
its own confidential information and which it warrants as providing
- 15 -
16
adequate protection of such information from unauthorized disclosure, copying or
use.
9.2 Definition of Confidential Information. In this Agreement,
"Confidential Information" means any confidential or proprietary information,
(whether disclosed or acquired directly or indirectly in writing, verbally or by
any other means, and whether disclosed or acquired before or after the date of
this Agreement or pursuant to this Agreement or in the course of performing this
Agreement), concerning the business of a Party, information related to the
Product, and information related to any Party's operations, processes, plans or
intentions, production information, know-how, data, formulae, expertise,
methodology, drawings, specifications, design rights, trade secrets, inventions,
market opportunities and business affairs, production methods, results of
testing of the Product, any market research and any new and novel combinations
thereof, but does not include information which:
(a) is in or comes into the public domain without any
breach of this Agreement by the receiving Party; or
(b) the receiving Party can show (i) was in its possession
or known to it by being recorded in its files prior to disclosure by the
disclosing Party; or (ii) to have been independently developed by it in the
course of work by its employees who have not had access to the Confidential
Information; or
(c) the receiving Party obtains or has available from a
source other than the disclosing Party without breach by the receiving Party or
such source of any obligation of confidentiality or non-use; or
(d) is disclosed by the receiving Party with the prior
written approval of the disclosing Party.
9.3 Exceptions. OraVax may divulge Confidential Information required
to be kept confidential pursuant to Section 12.1 in confidence to any
governmental authority to the extent required to obtain authorization for
marketing of the Product except that OraVax will provide adequate prior notice
to Xxxxx before providing such information.
9.4 Return of Documents. Upon termination or expiration as the case
may be of this Agreement, the receiving Party shall return to the disclosing
party promptly all documents and materials and copies thereof containing the
Confidential Information of the disclosing Party except that it may retain one
archival copy thereof for the sole purpose of being able to determine the scope
of its continuing obligations hereunder.
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17
SECTION 10. XXXXX'X WARRANTIES
10.1 Warranty of Xxxxx. Xxxxx does not warrant that Product Approval
will be obtained or, if obtained, that Product Approval will be obtained on a
timely basis. In the event Product Approval is obtained, Xxxxx warrants that the
Product will at the time of delivery comply with the specifications sanctioned
by the FDA in connection with Product Approval and will be manufactured in
accordance with the specifications outlined in Schedule 1 hereto and in a good
and workmanlike manner at a premises which complies with standards stipulated by
the relevant regulatory authorities in the Product Territory. OraVax agrees to
provide Xxxxx with written information relating to applicable laws, rules and
regulations in the Product Territory and in the event that such information
proves incorrect or incomplete, the warranty provided by Xxxxx herein shall not
apply and OraVax shall indemnify Xxxxx against all Damages accruing to Xxxxx and
arising through reliance by Xxxxx on such incorrect or incomplete information.
10.2 Authority for this Agreement. Each Party warrants and represents
that it has full power and authority to enter into this Agreement and to meet
the obligations hereunder.
10.3 No Infringement. Xxxxx warrants that as of the date of this
Agreement it is not aware of any infringement in the Product Territory of any
third party patents issued prior to the date of this Agreement by the Product
meeting the specifications in Schedule 1.
10.4 Indemnification. Xxxxx shall indemnify and keep indemnified and
hold OraVax, its employees, agents and contractors harmless against all Damages
arising for which OraVax or its employees, agents or contractors may be or
become liable which arise directly or indirectly from or in respect of any third
party alleging infringement of any patent issued prior to the date of this
Agreement, copyright, trademark or other intellectual property right of Xxxxx
relating to the Product. This Section 10.4 shall not apply with respect to cases
in which OraVax, its employees, agents or contractors, as the case may be, have
failed to handle and use the Product in accordance with the terms of this
Agreement or have otherwise acted negligently or in breach of this Agreement in
which case OraVax shall indemnify and keep indemnified and hold Xxxxx, its
affiliates, employees, agents and contractors harmless against Damages arising
for which Xxxxx or its affiliates, employees, agents or contractors may be or
become liable and arise directly or indirectly from or in respect of any third
party alleging infringement of any patent, copyright, trademark or other
intellectual property right due to such failure by OraVax to handle and use the
Product in accordance with the terms of this Agreement, or their negligence or
breach of this Agreement.
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18
SECTION 11. PRODUCT RECALL
11.1 Notice of Recall. OraVax shall inform Xxxxx forthwith by
telephone or facsimile transmission (immediately confirmed in writing) in the
event of any circumstances giving rise to a possible or actual recall of the
Product. Xxxxx shall inform OraVax forthwith by telephone or facsimile
transmission (immediately confirmed in writing) in the event of any
circumstances giving rise to a possible or actual recall of any batches of the
Product delivered to OraVax.
11.2 Right to Discontinue Sale of the Product. Xxxxx shall have the
right (irrespective of any power granted by law to the FDA or other authority in
the Product Territory) on the grounds of public health and safety to require
OraVax to discontinue sale of and recover some or all of the batches of the
Product specified by Xxxxx.
11.3 Notification to Purchasers of the Product. Where a product
recall has been initiated whether by the FDA or other authority or by Xxxxx
pursuant to Section 11.2, OraVax shall inform purchasers of the Product so
affected and shall require them to deliver or to make available for collection
all such stocks of the Product in their possession. OraVax shall ensure that
such stocks of the Product are collected and stored separately and securely in
premises controlled by OraVax pending further instructions from Xxxxx.
11.4 Reimbursement of Costs. Xxxxx shall reimburse OraVax for all
costs of any action taken pursuant to this Section 11 provided that where such
costs are caused by the negligence, breach of this Agreement or willful default
of OraVax, its employees or agents, OraVax shall bear such costs alone.
11.5 Notice of Product Recalls Outside the Territory. Xxxxx shall
notify OraVax immediately in the event a product recall of the Product has been
initiated by Xxxxx or any sub-contractor of Xxxxx in any country of the world
other than in the Product Territory.
SECTION 12. ADVERSE DRUG REPORTS
12.1 Adverse Drug Experience.
(a) OraVax shall conduct post marketing surveillance of
adverse events as required by the FDA. If OraVax receives any report of a
serious adverse drug experience (as described in Schedule 3) allegedly caused by
the Product, OraVax shall report the matter to the relevant regulatory
authorities in compliance with the laws and regulations of the Product Territory
covering licensed products and OraVax shall report to Xxxxx in a manner
consistent with the spontaneous
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19
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
adverse drug event (ADE) reporting procedure developed by Xxxxx for use by its
distributors forthwith by telephone or facsimile transmission (immediately
confirmed in writing). Xxxxx shall have responsibility for the notification of
regulatory authorities in the United Kingdom and in other countries in which the
Product is distributed, according to the statutory requirements in such
countries.
(b) If Xxxxx receives any report of a serious adverse drug
experience allegedly caused by the Product in any country of the world other
than the Product Territory, Xxxxx shall immediately advise OraVax accordingly.
(c) Xxxxx shall provide OraVax on a biannual basis with
written summaries of reports of adverse drug experiences that are not serious
but are allegedly caused by the Product in any country of the world other than
the Product Territory.
(d) OraVax shall provide Xxxxx on a biannual basis with
written summaries of reports of adverse drug experiences that are not serious
but allegedly caused by the Product in the Product Territory.
SECTION 13. PRODUCT LIABILITY
13.1 Indemnification of OraVax. Xxxxx shall indemnify and keep
indemnified and hold harmless OraVax, its employees, agents and contractors
against Damages for which OraVax shall or may be or become liable which arise
directly or indirectly from or in respect of any Product supplied by Xxxxx or on
behalf of Xxxxx to OraVax, or from such Product's, uses or effects, except those
Damages caused by the breach of this Agreement, negligence or wilful default of
OraVax its employees, agents or contractors.
13.2 Indemnification of Xxxxx. OraVax shall indemnify and keep
indemnified and hold harmless Xxxxx, its employees, agents and contractors
against all Damages arising for which Xxxxx shall or may be or become liable
which arise directly or indirectly from or in respect of the breach of this
Agreement, wilful default or negligence of OraVax, its employees, agents, or
contractors.
13.3 Product Liability Insurance. Each Party warrants that it has,
and will maintain for a period of four years following termination of this
Agreement, a product liability policy of insurance covering all risks liable to
be incurred under this Section for an amount not less than US[**] naming Xxxxx
as an insured party. In
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20
addition, OraVax shall effect at its own cost such insurance as may be required
by governmental or statutory authorities in the Product Territory. Each Party
will use its best endeavors not to do anything at any time which may disentitle
it to claim under such policy or which prejudices or in any manner adversely
affects its right to make a claim pursuant to such policy. Each Party must, upon
any reasonable request from the other Party, produce a certificate of currency
in respect of such policy. If at any time either Party fails to maintain such
policy the other Party shall be entitled to effect same on that party's behalf
and recover as a debt from that Party the costs incurred in so doing and at its
option terminate this Agreement pursuant to Section 14.1(b)(iii). Each Party
must advise the other in writing within 48 hours of it becoming aware of the
occurrence of any event relating to the Product which could or might lead to a
claim under, or the cancellation of, such policy for any reason whatsoever.
13.4 Notice of Claims. The indemnities provided in this Section 13
and Section 10.4 hereof shall apply only if the indemnified Party shall promptly
notify the indemnifying Party in writing of any claims, proceedings, or other
actions or the threat thereof in respect of which indemnification may be sought.
The indemnified Party shall reasonably cooperate with the indemnifying Party in
connection with defending or settling any claim, proceeding or other action in
respect of which indemnification may be sought. No settlement of any claim,
proceeding or other action or threat thereof for which indemnification is sought
shall be made without the prior written approval of the indemnifying Party. The
indemnifying Party will have the sole control over the defense and/or settlement
of any claim, proceeding, or other action for which indemnification is sought,
subject to the indemnified Party's right to select and use its own counsel and
the indemnified Party's sole cost and expense.
SECTION 14. TERMINATION
14.1 This Agreement may be terminated:
(a) By either Party without cause by giving to the other
Party;
(i) At least six (6) months written notice
expiring with the expiration of the Initial Period; and thereafter
(ii) At least six (6) months written notice,
expiring with the expiration of the current Additional Period.
(b) By the Party not affected by giving to the other Party
written notice to terminate on the date specified in the notice should any of
the following events occur, namely:
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21
(i) The other Party becoming insolvent or having
a receiver appointed of its assets, or execution or distress levied upon its
assets;
(ii) An order being made or a resolution being
passed for winding-up or liquidation of the other Party;
(iii) Failure of the other Party to observe any
of the terms hereof to a material and significant extent and to remedy the same
within the period specified in a notice given by the aggrieved Party to the
Party in default calling for remedy, being a period not less than thirty (30)
days;
(iv) The other Party's failure to perform its
duties hereunder for a continuous period of three (3) months or for a total
period of six (6) months in any period of twelve calendar months due to a cause
beyond the reasonable control of the Party failing to perform, including fire,
flood, riot, breakdown of machinery, industrial action, shortage of materials,
epidemic, government action or war;
(c) By either Party upon three (3) months, written notice
to the other Party;
(i) prior to the first launch of the Product in
the Territory, provided that such termination is due to the legitimate failure
of the Product for clinical or regulatory reasons, or
(ii) In the event that the GM falls below the
current GM Target as contemplated in accordance with the prior mutual agreement
of the Parties.
(d) In accordance with Section 2.4.
14.2 In the event of this Agreement being terminated, OraVax
undertakes to reasonably co-operate with Xxxxx and any successor of OraVax
appointed by Xxxxx and (if applicable) any other distributor of the Products in
the Product Territory with a view to ensuring an orderly transfer of any
licenses and distribution responsibilities.
14.3 On termination or expiration of this Agreement, as the case may
be:
(a) OraVax shall provide Xxxxx with full particulars of all
unsold Product (including quantities of each Product, the dates on which the
Product was delivered) in its possession. Xxxxx shall be entitled at its
discretion to purchase from OraVax at the price actually paid by OraVax all or
any of the unsold Product.
(b) If so requested by Xxxxx, OraVax shall arrange for
delivery of the Product purchased by Xxxxx pursuant to paragraph (a) of this
Section 14.3 to such
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22
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
destination or destinations as may be designated by Xxxxx. All delivery
arrangements shall be subject to the prior approval of Xxxxx. Reasonable costs
of freight and insurance for such delivery shall be paid by Xxxxx.
(c) Any Product in respect of which Xxxxx has notified
OraVax in writing that it does not wish to repurchase pursuant to paragraph (a)
of this Section 14.3, may be sold by OraVax within six (6) months after
termination, in which case the terms of this Agreement or such of them as are
relevant shall continue to operate until the remaining Product has been sold or
the period of six (6) months expires, whichever first occurs. Any remaining
unsold Product may be collected by Xxxxx after such six month period, and Xxxxx
shall pay to OraVax [**] percent of any amounts that Xxxxx receives in respect
of such Product net of expenses of collection and sale.
(d) OraVax shall promptly forward to Xxxxx, at OraVax's
cost, all Confidential Information and all promotional and advertising materials
and all technical information relating to the Product then in OraVax's
possession; and OraVax shall not keep any copies of such materials and
information, subject to the provisions of Section 9.4.
(e) OraVax shall not be entitled to compensation for
goodwill which may have accrued to the marketing of the Product in the Product
Territory, and Xxxxx may make such other arrangements for marketing the Product
as it may deem expedient in order to preserve the goodwill in such marketing
exercise.
(f) OraVax shall have a [**] right of first refusal with
respect to any similar agreement that Xxxxx desires to enter into if the
proposed terms of such agreement are more favorable than those in existence
under this Agreement at the time of termination; provided, however, that this
Section 14.3(f) shall not apply in the event that this Agreement is terminated
by Xxxxx pursuant to Section 14.1(b)(iv), on account of a material breach by
OraVax of its obligations under this Agreement.
14.4 The termination of this Agreement shall be without prejudice to
the rights, obligations and remedies of the Parties accrued up to the date of
such termination or continuing thereafter.
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23
SECTION 15. ANCILLARY PROVISIONS
15.1 Assignment by Xxxxx. Nothing herein shall restrict Xxxxx'x right
to assign this Agreement or the rights or obligations hereunder to a third
party, provided that such assignment does not have the effect of compromising
any material rights and privileges granted to OraVax herewith.
15.2 Subdistributors. OraVax shall not sell the Product through a
sales agent or sub-distributor except with the prior written consent of Xxxxx to
any sub-distributor unless the distributor is a wholly-owned subsidiary of
OraVax. Sales of Product by any such distributor shall be deemed a sale by
OraVax. OraVax shall be and remain responsible for the acts and omissions of any
such distributor in relation to this Agreement and the resale of the Product.
15.3 Entire Agreement. This Agreement embodies all the terms binding
between the Parties hereto and replaces all previous representations or
proposals (whether written or oral) not embodied herein. Amendments hereto shall
not come into operation until duly embodied in any amending Agreement properly
executed on behalf of both Parties hereto.
15.4 No Waivers. No waiver by either Party of any default in the
strict and literal performance of or any compliance with any provision,
condition or requirement contained in this Agreement shall be deemed to be a
waiver of strict and literal performance of and compliance with any other
provision, condition or requirement contained in this Agreement nor to be a
waiver or in any manner a release of the other Party from strict compliance with
any provision, condition or requirement in the future. Nor shall any delay or
omission of any party to exercise any right under this Agreement in any manner
impair the exercise of any such right accruing to it thereafter. Unless
otherwise expressly stated, no remedy granted in this Agreement to either Party
shall be deemed to exclude any other remedy which would otherwise be available.
Each Party shall bear its own legal costs and expenses of and incidental to the
preparation of this Agreement.
15.5 Governing Law. The Parties will attempt to resolve all disputes
under this Agreement in a friendly and constructive manner, and any such
disputes remaining unresolved shall be governed by the laws of the State of New
York, U.S.A., without regard to the conflict of laws and principles thereof.
15.6 Survival. Sections 7.9, 8.1, 9, 11, 12, 13, 14.2, 14.3 and 14.4
shall survive termination.
15.7 Assignment by OraVax. OraVax shall have no rights to assign this
Agreement or the rights and obligations hereunder except (i) with the prior
written consent of Xxxxx or (ii) to a successor business entity which acquires
or encompasses
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24
substantially all the business and assets of OraVax. A change in ownership or
control of OraVax shall not be deemed an assignment of this Agreement.
15.8 Force Majeure. A Party shall not be liable for any failure to
perform or observe any term of this Agreement if performance or observance has
been delayed, hindered, restricted or prevented by any circumstance not within
the direct control of such Party, including without limiting the generality of
the foregoing, Acts of God, strikes, lock-outs or other industrial disturbances,
war, hostilities or the threat or apprehension thereof or any interruption to
the supply of materials or information or any accident or breakdown of machinery
or the making of emergency or essential repairs thereto or compliance with any
valid order of any governmental or public authority' and the time or times for
performance of the obligations of the respective Parties to be performed herein
shall be extended by a period equal to each such period of delay, provided that
such Party shall forthwith give notice to the other Party in accordance with the
provisions of this Agreement and shall endeavor to remove or remedy the cause
thereof with all due diligence and expedition. Clause 14.1(b)(iv) shall apply.
SECTION 16. NOTICES
16.1 Where this Agreement requires a written notice, the notice may
be given by post, personal delivery or facsimile transmission to the other Party
and is to be marked to the attention of the person from time to time designated
for this purpose by the other Party. The signatories to this Agreement are the
persons initially designated for this purpose and their respective initial
addresses and facsimile numbers are set - out hereunder:
Xxxxx Medical Limited
Xxxxx House, Regent Park
Xxxxxxxx Xxxx, Xxxxxxxxxxx
Xxxxxx XX00 0XX
Xxxxxx Xxxxxxx
Facsimile 01372 364018
OraVax, Inc.
00 Xxxxxx Xxxxxx
Xxxxxxxxx, XX 00000, X. S. A.
Facsimile + 0 (000) 000 0000
16.2 No written notice is to be effective until received, or deemed
to be received by the other Party as follows:
(a) in the case of personal delivery, upon delivery;
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25
(b) in the case of a letter, on the fifth business day
after posting (business days to be determined according to the place of
receipt); and
(c) in the case of a facsimile transmission, on the
business day on which it is dispatched, or, if dispatched on a non-business day,
or after 5 pm on a business day then on the next business day (times and
business days to be determined according to the place of receipt) after the day
on which it is dispatched. A record from the dispatching facsimile machine
detailing the time and date of the transmission shall be evidence of
transmission, unless proved to the contrary.
IN WITNESS WHEREOF the Parties hereto have executed this Agreement as
of the date first written above.
XXXXX MEDICAL LIMITED
By: /s/ Xxxx Xxxxxx
---------------------
Title: European Director
ORAVAX, INC.
By: /s/ Xxxxx X. Xxxxxxx
-----------------------
Xxxxx X. Xxxxxxx
Vice President and
Chief Financial Officer
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26
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
SCHEDULE 1
OUTLINE OF CLINICAL TRIAL AND RESPECTIVE RESPONSIBILITIES
(Terms in the Agreement shall, if a conflict arises, apply
instead of any terms in this Schedule or any documents
contemplated by this Schedule)
CLINICAL TRIALS WORKSCOPE
CLINICAL PROTOCOL AND INVESTIGATOR'S BROCHURE
- Xxxxx has prepared a clinical protocol for a pivotal trial of their
YF 17D vaccine in the United States [**].
- [**] Xxxxx and OraVax will [**] taking into consideration input
previously provided [**].
- An Investigator's Drug Brochure (IDB) will be prepared by Xxxxx and a
copy provided to OraVax.
- The clinical protocol and IDB will be reviewed and approved by the
Heads, Clinical and Regulatory Affairs at Xxxxx and OraVax.
- Xxxxx will file these documents as part of an IND submission to FDA
[**].
IND
- Xxxxx will be responsible for submission of the IND to FDA [**].
- Xxxxx will provide a complete draft copy of the IND to OraVax two
weeks prior to submission to FDA.
OPERATIONAL ASPECTS OF THE CLINICAL TRIAL(S)
GENERAL
- OraVax and Xxxxx will mutually agree in advance on the respective
roles of the Companies in operational aspects of the clinical trials,
listed below. The underlying principle is that OraVax is willing to
independently undertake all components of the trial(s), but is
pleased to collaborate on any and all these components, depending
entirely upon the capabilities and interests of Xxxxx in specific
aspects of the trial(s). The details of such collaborations and the
27
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
responsibilities of the respective parties shall be worked out in
meetings between the partners and documented in a Clinical Action
Plan.
CLINICAL ACTION PLAN
[**], a Clinical Action Plan will be prepared that details the operational
activities required to implement the trial(s), the parties responsible for these
activities, and realistic timelines. The Clinical Action Plan will be approved
by the Head(s), Clinical Affairs and Regulatory affairs, OraVax and Xxxxx.
- All aspects of the clinical trial(s) will be performed according to
guidelines and regulations for GCP, as specified in the FDA Code of
Federal Regulations 21 CFR.
- Approved Standard Operating Procedures (SOPs) will be in place for
all aspects of the clinical trial(s).
- Study documentation will be sufficient to withstand future
inspections by the FDA.
- The overall budget for the clinical trial will be approved by OraVax
and Xxxxx.
- The Clinical Action Plan will contain the following information:
-Specific responsibilities of OraVax and Xxxxx
-Completion of Clinical Protocol, IDB, Pharmacy Brochure,
Study-specific SOPs
-Number of subjects planned
-Number of centers
-Qualification of investigators, archiving CV's, and form
1572's
-Confidentiality agreements with investigators
-Start and finish dates
-Case Report Form preparation
-Regulatory and Ethics Committee approval
-Shipment, distribution and storage of clinical trials
material
-Financial agreements and method of payment
-Investigator's and study coordinator meetings
-Subject enrollment
-Clinical and medical monitoring
-SAE reporting
-Data base management
-Data cleaning procedures
-Statistical analyses
-Serological testing (Baseline flavivirus serology, YF
neutralization test)
-Back-titration of vaccine
-Other outcome and safety laboratory measurements
28
-Clinical study report
-Publications, authorship
- Clinical trial sites and investigators with experience in conducting
clinical trials will be identified. Insofar as possible, these sites
will be geographically clustered in New England to facilitate
clinical monitoring. Sites will be travel clinics or physicians
having prior approval to administer YF vaccine.
TRIAL IMPLEMENTATION
- OraVax will implement those parts of the Clinical Action Plan that
are specified as OraVax's responsibilities.
- Xxxxx will implement those parts of the Clinical Action Plan that are
specified as Xxxxx' responsibilities.
- Trial(s) will be implemented such that no undue delays or cost
overruns occur, in the judgment of both parties.
29
Confidential materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
SCHEDULE 2
SALES TARGETS
OraVax represents that it is reasonably able to and shall seek to
achieve no less than [**] and [**] of the U.S. private market within the [**]
years, respectively, following commencement of sales of the Product in the
Product Territory.
30
SCHEDULE 3
SPONTANEOUS ADVERSE DRUG EVENT (ADE) REPORTING PROCEDURE-
INDIVIDUAL CASE REPORTS
All Adverse Event (ADE) reports to the Distributor should be directed to a named
individual, nominated by the Distributor. This nominated contact will be
responsible for all communication between the Distributor and the Supplier's
central ADE reporting procedure.
Standard form ADE1/C may be used to record the initial report of an adverse
experience. As much information as possible about the ADE should be requested
and recorded.
Each ADE Report should be assigned an identifying number by the nominated
contact. All ADEs reported to the Distributor are to be forwarded as soon as
possible, i.e. on the same working day, but in any event within 3 working days,
by fax or telephone to the Product Safety Manager, at the Supplier's premises.
The Distributor should follow up the ADE report to obtain additional details,
and where the reporter is a non health professional, medical confirmation. Form
ADE1/D may be used to obtain follow-up information and written confirmation of
the initial report.
On receipt of the initial report from the Distributor the Product Safety Manager
will log it into Product Safety's centralized procedure, and assign a central
reference number consisting of 3 letters (DIS) the last 2 digits of the year,
and a sequential number. The Product Safety Manager will acknowledge receipt of
the report and advise the Distributor of the central reference number assigned.
The Product Safety Manager will submit the ADE report to Regulatory Authorities
in all countries where the product is marketed, including the Regulatory
Authority in the country where the report originated, according to regulatory
requirements. The Distributor will be copied on any correspondence with the
local Regulatory Authority.
The Distributor will forward to the Product Safety Manager, as soon as possible
after receipt, the reporter's written confirmation of the event and any
additional information, clearly identified with the central reference number.
ADE reports will be notified to the local Regulatory authority in other markets
if appropriate, according to their requirements. The Distributor will be copies
on any correspondence in the local market.
A summary of the procedure, and forms ADE1/C and ADE1/D are attached.
The name of the nominated contact should be forwarded to Product Safety as soon
as possible so that other Pharmacovigilance issues of mutual interest can be
discussed and agreed.
31
SPONTANEOUS ADVERSE EVENT (ADE) REPORTING PROCEDURE
ADE report from e.g. medic, pharmacist, customer, regulatory authority
NOMINATED CONTACT AT DISTRIBUTOR
- Report ADE to Product Safety Manager at Xxxxx Medical Ltd. on form
ADE1/C as soon as possible, (same day if possible but within a
maximum of 3 working days, Fax No. +441372 364163, Tel No. +441372
364164).
- Request written confirmation of ADE from reporter/prescribing doctor.
Form ADE1/D may be used for this purpose.
PRODUCT SAFETY, Xxxxx Medical Ltd.
- Assign central reference number to ADE1/C
- Acknowledge receipt and advise assigned central reference number.
- Obtain Xxxxx Medical assessment on ADE2A form, is ADE serious?
Unexpected? Associated with product administration?
- In accordance with medical assessment and regulatory requirements
notify Regulatory authorities, (including Regulatory Authority in
country of origin) of ADE
- Notify the Local Regulatory Authority, as appropriate, of ADEs
occurring in other countries.
- Copy the Distributor on any correspondence with the Local Regulatory
Authority.
NOMINATED CONTACT, DISTRIBUTOR
- Fax all follow-up information, clearly identified with assigned
central reference number, to Product Safety Manager, Xxxxx Medical
Ltd.
- Notify Product Safety Manager at Xxxxx Medical Ltd. when considered
no further information forthcoming and case is closed.
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FORM ADE1/C/V
ADVERSE EXPERIENCE REPORT (Vaccine)
1 Caller 2 Clinical to contact (if name supplied) Product Safety use
Dr/Mr/Mrs/Ms Dr/Mr/Mrs/Ms
AE No:
Address Address
Receipt Date:
_____/____/____
DD MM YY
Tel___________ Fax___________ Tel___________ Fax___________
Position_____________________ Alert report No: _______
3 Was call an Enquiry? ___ Report of AE? ___ Other? ___
4 Vaccine:________________ Date of Vacc.:____/____/____ B/No:_________________
Try course/Booster? ___________ If try, which dose? _________ Date of last vaccination:___/___/___
5 Patient Initials ____ M/F DOB or Age (elderly/infant/child, if not precisely known) ____
Concurrent vaccines/medication:
Medical history-Any events after earlier doses/any allergies?
6 Description of event Onset time (either date or time after admin. of vaccine):________________
7 Action taken (state if none or unknown)
Treatment given?
Was patient admitted into hospital/hospital admission prolonged?
8 Outcome Disabled/Incapacitated ____ Recovered ____
Fatal ____ Continuing ____
9 Does reporter consider that the adverse event was related to the vaccine?
Any other explanation for events?
Company Nominated Contact's Signature:______________________ Date:___/___/___ (DD/MM/YY)
33
FORM ADE1/D/V
ADVERSE EXPERIENCE REPORT (MARKETED VACCINE)
DESCRIPTION OF ADVERSE EXPERIENCE (including relevant investigations and
treatment required):
DIAGNOSIS:
MOST SIGNIFICANT SYMPTOM:
AE onset date: ____/____/____ time to onset: ______ Date AE resolved: ____/____/____
DD MM YY (if less than 24hrs) DD MM YY
SUSPECT PRODUCT:_________________ B/No.____________ storage conditions:__________
Date of vaccination: ____/____/____ Dose:________ Route/Site:______ Indication:__________
DD MM YY
Course: Try ___ booster ___ If try, which dose:______ Date(s) of prev. dose(s): ____/____/___
DD MM YY
Previous exposure? Yes ___ NO ___ AE experienced with previous exposure? Yes ___ No ___
If YES, describe:_____________________________________________________________________________
PATIENT'S DETAILS:
Patient Initials:______ Sex: M ___ F ___ Pregnant: Yes ___ No ___
Patient's date of birth: ____/____/____ or Age:_____ If under 6 yrs, no. of siblings:_____
--
DD MM YY
Ethnic Origin:______________ (Caucasian, Asian, etc.) Weight:______ Height:_______
Relevant Medical History, including Allergies:
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
CONCOMITANT MEDICATION DETAILS (any medication taken in 3 months prior to AE
onset)
Medication Name Dose Frequency Route/ Indication Dates
include batch or lot no. if known) Site start stop
------------------------------------------------------------------------------------------------------------------------------------
34
FORM ADE1/D/V AE No. ___________________________
ACTION TAKEN (CHECK ALL THAT APPLY)
required intervention ____
specify:_______________________________________________________________________________________
_______________________________________________________________________________________________
_______________________________________________________________________________________________
new ____
hospitalization From:____/____/____ To:____/____/____
DD MM YY DD MM YY
prolonged ____
OUTCOME (CHECK ALL THAT APPLY)
disability ____
life threatening ____
congenital anomaly ____
resolved ____
resolving ____
continues ____
unknown ____
fatal ____
date died:____/____/____ cause:______________________ confirmed by autopsy ____
ASSESSMENT
Relationship of AE to Drug: none ____ unlikely ____ possible ___
probable ____ highly probable ____ unclassifie ___
mild ____ moderate ____ severe ___
REPORTER'S DETAILS: RESPONSIBLE PHYSICIAN'S DETAILS:
(if different)
Name:__________________________________________ _______________________________________
Occupation:_____________________________________ _______________________________________
Address:________________________________________ _______________________________________
________________________________________ _______________________________________
Country:________________________________________ _______________________________________
Telephone:______________________________________ _______________________________________
Has the Regulatory Authority been notified? Yes __ NO __ If YES, Date sent ____/____/____ and
ref. No. ___________ DD MM YY
HEALTH PROFESSIONAL'S SIGNATURE:____________________________ Date:____/____/____
Please state: Physician/Dentist/Pharmacist/Nurse/Coroner DD MM YY
