Exhibit 10.31
SUPPLY AGREEMENT - TRILOSTANE
STEROID SpA
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SIGNATORIES TO THE SUPPLY AGREEMENT:
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This Supply Agreement (the "Agreement"), by
and between:
Stegram Pharmaceuticals Ltd., with
principal executive offices located at 44
Broomfield Drive, Billingshurst, Sussex
RH14 9TN, UK ("Stegram")
Bioenvision, Inc., with principal executive
offices located at 345 Park Avenue,
41st Floor, New York, New York 10154, USA
("Bioenvision")
Dechra Ltd., with principal executive
offices located at Jamage Industrial
Estate, Talke Pits, Stoke on Trent,
Staffordshire, ST7 1XW, UK ("Dechra")
AND
Steroid SpA, Viale Spagna 156, 20093,
Cologno Monzese MI, Italy ("Steroid"),
is made and effective as of 12th day of
August 2005 (the "Commencement Date").
WHEREAS:
(1)
Stegram is the
proprietor of patents and technical information
relating to the development and uses of a dehydrogenase
inhibitor
and receptor blocker and related compounds, including
trilostane,
hereinafter referred to as "the Product".
(2)
Bioenvision obtained
certain rights to practice the inventions of
such patents and technical information from Stegram, pursuant
to
that certain Co-Development Agreement, dated 17th July 1998 (as
amended, the "Co-Development Agreement").
(3)
Dechra obtained
certain rights to the Product for use in the
veterinary market from Stegram, pursuant to that certain
Manufacturing and Distribution Agreement between Stegram and
Arnolds
Veterinary Products, a trading division of Dechra, dated 10
December
2001 and pursuant to that certain Joinder, dated 26 February
2004,
by and between Stegram, Bioenvision and Arnolds.
(4)
Steroid has
manufactured the Product (as defined in Section 1 below)
at the direction and desire of Stegram and desires to continue
to
manufacture Product at the direction and desire of Stegram,
Bioenvision and Dechra.
(5)
Stegram, Bioenvision
and Dechra desire for Steroid to continue to
manufacture Product on their respective behalf pursuant to the
terms
of this Agreement.
(6)
Bioenvision, Dechra
and Steroid acknowledge that title to Industrial
Property Rights pertaining to the Product, which include
proprietary
information on synthesis, process, analytical, technical,
commercial
information, know-how and data relating to the manufacture and
commercial exploitation of the Product, is and remains at all
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times the exclusive property of Stegram, excepting such
information
as is transferred under the terms of the abovementioned
Agreements
or is transferred by subsequent Agreements which shall be at
the
sole discretion of Stegram.
(7)
This Agreement is a
non-exclusive Agreement with Steroid.
1.
DEFINITIONS AND INTERPRETATION
1.1 In this
Agreement, unless the context requires otherwise:
"Agreement" shall be this Supply Agreement and its associated
Schedules.
"Buffer Stock" means a quantity of Product maintained on
Steroid's
inventory and at Steroid's expense as a contingency to meet
supply
requirements in the event of a manufactured batch failing to comply
with
the Specification, or in the event of other unforeseen and/or
emergency
requirements.
"Bulk Product" means Product in a form as manufactured by
contractor to
the Specification set out in Schedule 2 and prior to its
formulation
into medicinal Finished Product.
"Certificate of Analysis" means a document certifying the results
of
analysis performed on the Product following manufacture in order
to
determine compliance with the Specification (set out in Schedule 2)
for
the Product. Analytical results shall be reported on the
Certificate of
Analysis in a manner which is acceptable to the relevant
regulatory
authorities. The Certificate of Analysis shall also show the
Product
batch number to which the analysis refers, the dispatched quantity
of
Product produced as the batch, and the date of manufacture of the
batch.
"Commencement date"
shall be the date of this Agreement.
"Designee" means a Party acting on behalf of or in lieu of another
Party
or the subsidiary of a Party acting on behalf of or in lieu of the
Party
to this Agreement.
"Drug Master File"
means a description of the Product, its manufacture,
its Specification and other information relevant to its production
by
Steroid including such information about Steroid and Steroid's
production operation as is relevant to satisfy regulatory
authorities as
to the fitness of the Product as manufactured by Steroid for use of
the
Product in human and veterinary medicine. A European Drug Master
File
will comprise an "Open Part" and a "Closed Part" or other
designations
with the same meanings. "Open Part" means that Information
contained
within a regulatory submission which is in principle accessible by
the
public. "Closed Part" means that Information contained within a
regulatory submission which is not available for public disclosure
or
use and shall include but not be limited to a description of
the
manufacturing process, Product specification and methods of
analysis,
raw materials and intermediates and their specifications and
methods of
analysis, a description of possible impurities, stability test data
and
packaging and labelling. The Information contained in the Open Part
and
the Closed Part of a European Drug Master File or any other Drug
Master
File the format of which includes a Closed Part or
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confidential section, shall be authorised by Stegram. Bioenvision
and
Dechra shall be responsible for ensuring that such Information
is
included in the Closed Part and that the Closed Part and Open Part
are
clearly marked in the Drug Master File. A United States Drug Master
File
is confidential in its entirety and in this regard is therefore
equivalent to the Closed Part of a European Drug Master File.
"Europe" means the countries of the European Union, Switzerland
and
Norway.
"Finished Product" means Product formulated into a dosage form for
use
as a human or veterinary medicine.
"(current) Good Manufacturing Practice" means that the
batchwise
manufacturing of the Product shall be conducted under conditions
of
current Good Manufacturing Practice as required by but not limited
to
the pharmaceutical industry regulatory authorities in Europe, the
United
States of America and Japan.
"Industrial Property Rights" means all know-how, copyright,
trademarks,
patents, designs, information and documentation, including but
not
limited to the Specification, drawings and Information relating
to
manufacture and analysis, assembly and use of the Product.
"Information" means any scientific, statistical, commercial or
technical
information, know-how or data which may be disclosed or
communicated by
any Party to Steroid directly or indirectly, verbally, or by any
other
means, which has been confirmed in writing.
"Nominee" means a Person nominated by Stegram to conduct certain
aspects
of Stegram's business on behalf and with consent of Stegram as
expressly
set forth in this Agreement.
Stegram, at its sole discretion, appoints as Nominees Michael
Anthony
Parrish, trading as
Parrish Business Developments, with offices located
at 2 Whitegates, Longhorsley, Morpeth, Northumberland NE65 8UJ,
UK
("PBD") and Keane Analytical Limited, with offices located at
Vallum
Farm, Military Road, East Wallhouses, Newcastle upon Tyne NE18 0LL,
UK
("Keane") and Micron Technologies Limited, with offices located
at
Crossways Boulevard, Crossways, Dartford, Kent DA2 6QY, UK
("Micron").
Notwithstanding any other provision of this Agreement to the
contrary,
Stegram shall remain fully responsible for each and every
obligation
performed on its behalf pursuant to this Agreement by its Nominee
as if
each such obligation had been performed directly by Stegram.
"Parties" means
collectively Stegram, Bioenvision and Dechra and "Party"
means one of these.
"Person" means any individual, firm, unincorporated association,
body
corporate or any other entity.
"Price" means the price payable for the Product as set out in
Schedule
3.
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"Product" means the product described in Schedule 1 and all
modifications developments and improvements relating thereto.
"Purchase Terms" means the purchase terms set out in Schedule
4.
"Qualified Person" means a person who fulfils the minimum
conditions of
scientific and technical qualifications referred to in Article 23
of EEC
(European Economic Community) Directive 75/319/EEC and Article 31
of EEC
Directive 81/851/EEC or qualifications as may be ordered by
subsequent
EEC Directives from time to time.
"Quality Audit" means an inspection undertaken by any Party hereto
or
their respective Designee(s) or Nominee(s) by prior arrangement at
any
reasonable time at Steroid's premises for the purposes of
confirmation
of regulatory compliance and quality assurance. Steroid undertakes
to
make available to any such Party or its respective Designee or
Nominee:
personnel, documentation, factory facilities, laboratories and
other
sources of information, relating to production, quality assurance
and
quality control of the Product.
"Reworked Product" means Product which has not complied with
the
required standard of quality including but not limited to the
Specification, and is purified in order to meet the required
standard of
quality by Steroid's application of a chemical operation typified
by but
not limited to recrystallisation.
"Schedule" means Schedules which constitute part of this Agreement
and
are designated as:
Schedule 1 -
Product
Schedule 2 -
Specification
Schedule 3 -
Price and Quantity of Product
Schedule 4 -
Purchase Terms
Schedule 5 -
Record of additions, deletions, or
amendments to Supply Agreement and
Schedules (with file references to
written consents) and procedural
agreements made with the Parties or
their respective Designees or Nominees
"Specification" means the specification of the Product set out
in
Schedule 2 or any other specification determined by Stegram.
"Stage 1" means
(17a)-17-hydroxy-2-(hydroxymethylene)androst-4-en-3-one
"Stage 2" means (17a)-androsta-2,4-dieno(2,3,d)isoxazol-17-ol
"Stage 3" means (4a
,5a,17a)-4,5-epoxyandrost-2-eno-(2,3,d)-isoxazol-17-ol (designated
by
Chemical Abstracts Service Registry Number 20051-76-7)
"Term" means the period of 5 years commencing on the date of
this
Agreement.
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"Validation Batch" means a batch of Product, data from which is
used to
demonstrate the efficacy of the manufacturing process, the
reproducibility of Product quality, Product stability, and
other
parameters which may be required by regulatory authorities in order
to
grant approval of the manufacturing process and Product
quality.
"Writing" and "Written" mean transmission of information by means
of
black or blue ink applied by hand or machine to paper by the sender
and
signed and dated by the sender. The definition expressly
excludes
information sent by facsimile or electronic mail (e-mail) by means
of
the internet unless otherwise authorised by the Parties.
"Year" means the period of 12 (twelve) months from the date of
this
Agreement and each subsequent consecutive period of 12 (twelve)
months
during the period of this Agreement.
1.2
Reference to a clause, paragraph or
Schedule is to a clause, paragraph or
Schedule of or to this Agreement unless the
context requires otherwise.
1.3
Reference to any gender includes the other
gender and words denoting the
singular include the plural and vice versa
unless the context requires
otherwise.
1.4
Reference to a statutory provision includes
a reference to that statutory
provision as from time to time amended
extended or re-enacted and any
regulations made under it.
1.5
The headings in this agreement are for ease
of reference only and shall not
affect its construction or
interpretation.
2.
CONTACTS
2.1
Contact names, addresses, communications
numbers and e-mail addresses of the
Parties, their authorized Nominees and
Designees under the terms of this
Agreement, and Steroid, are listed below.
Also below are certain general
obligations of the Parties pursuant to this
Agreement, subject to the terms and
conditions set forth in this Agreement in
their entirety.
Under the terms of this Agreement the
Parties or their authorized Nominees and
Designees under the terms of this
Agreement, and Steroid, shall perform
individual duties including but not
necessarily limited to those described in
this Agreement:
Bioenvision
Bioenvision, either directly or through one
or more of its subsidiaries, markets
Finished Product for use in human medicine
and shall provide regular quantity
requirement forecasts for the Product to
Stegram and orders for the product to
Steroid and payment in UK pounds sterling
direct to Steroid for the provision of
Product under the terms of this
Agreement.
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Contact Hugh Griffith
Telephone
131-248-3600
Fax
131-248-3300
e-mail
hughgriffith@bioenvision.com
Dechra Ltd.
Dechra, either directly or through one or
more of its trading divisions, markets
Finished Product for use in veterinary
medicine and shall provide regular
quantity requirement forecasts for the
Product to Stegram and orders for the
Product to Steroid and payment in UK pounds
sterling direct to Steroid for the
provision of Product under the terms of
this Agreement.
Arnolds Veterinary Products, Cartmel Drive,
Harlescott, Shrewsbury, Shropshire
SY1 3TB, UK (hereinafter referred to as
"Arnolds"). Arnolds is a trading
division and Designee of Dechra Ltd.
Contact
Ed Torr
Telephone 1743-44
1632
Fax
1743-462111
e-mail
ed.torr@dechra.com
Dales Pharmaceuticals, Snaygill Industrial
Estate, Keighley Road, Skipton, BD23
2RW, UK (hereinafter referred to as
"Dales"). Dales is a company engaged in the
production of pharmaceutical dosage forms
in which capacity Dales acts as a
manufacturing contractor. Dales may also
from time to time place orders with
Steroid for the Product on behalf of any of
the Parties. Dales is a trading
division and Designee of Dechra Ltd.
Dales
Mike Annice
Telephone
1756-791311
Fax
1756-798604
e-mail
m.annice@dalespharma.com
Keane Analytical Limited, Vallum Farm,
Military Road, East Wallhouses, Newcastle
upon Tyne NE18 0LL, UK (hereinafter
referred to as "Keane"). Keane is a company
engaged in the business of chemical
analysis and quality control and has been
appointed by Stegram to conduct independent
quality control of the Product on
behalf of Stegram. Keane is a Nominee of
Stegram.
Keane
Dr Jane Riseborough
Telephone
1434-672542
Fax
1434-672543
e-mail
j.riseborough@keane-analytical.co.uk
Micron Technologies Limited, Crossways
Boulevard, Crossways, Dartford, Kent DA2
6QY, UK (hereinafter referred to as
"Micron"). On behalf of Stegram and in its
capacity as Nominee of Stegram, Micron
Technologies shall micronise bulk Product
to a particle size and particle size
distribution specification as determined by
Stegram, conduct appropriate analysis to
ensure compliance with the particle
size and particle size distribution
specification as determined by Stegram and
arrange shipment as required by one of the
Parties or a Nominee during the term
of this Agreement.
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Micron
Hazel Osborne
Telephone
1322-425200
Fax
1322-425201
e-mail
hosborn@microntech.com
Michael Anthony Parrish trading as Parrish
Business Developments, 2 Whitegates,
Longhorsley, Morpeth, Northumberland NE65
8UJ, UK (hereinafter referred to as
"PBD"). Michael Anthony Parrish is a
Nominee of Stegram.
Contact
Dr Michael Parrish
Telephone
1670-788432
Fax
1670-788620
e-mail
mparrish@britishlibrary.net
Stegram
Stegram is the proprietor of a business
engaged in but not limited to the sale
of the Product. Title to industrial
Property Rights pertaining to the Product,
which include proprietary information on
synthesis, process, analytical,
technical, commercial information, know-how
and data relating to the manufacture
and commercial exploitation of the Product,
is and remains at all times the
exclusive property of Stegram, excepting
such information as is transferred
under the terms of the abovementioned
Agreements (Section "Whereas") or is
transferred by subsequent Agreements which
shall be at the sole discretion of
Stegram.
Contact
Dr George Margetts
Telephone
1403-783214
Fax
1403-783214
e-mail
gmargetts@doctors.org.uk
Steroid
Steroid shall provide the services set
forth in this Agreement, including,
without limitation, the following:
manufacture of Product in bulk form at the
address set forth in the section
`Signatories to the Supply Agreement' solely
for the Parties under conditions of current
Good Manufacturing Practice to a
Specification provided by Stegram, validate
analytical methodologies provided by
Stegram, conduct analyses on the Product
and its intermediates as required by
Stegram for the purposes of quality
control, conduct storage stability testing
of the Product, provide samples of Product
and its intermediates, and store
Product all pursuant to applicable current
Good Manufacturing Practice and other
applicable regulatory requirements. Steroid
shall also arrange shipment of
Product and shall invoice direct Dechra or
Bioenvision or Stegram or Dales, as
the case may be. Under the terms of the
Agreement Steroid may conduct
manufacturing process development and
analytical methodology development on the
Product only in collaboration with and by
written consent of Stegram.
Contact
Dr Philip Payne
Telephone
02-2541731
Fax
02-26700452
e-mail
phillip_payne@steroid.it
Each Party and/or Nominee shall have the
opportunity to change or modify the
contact information set forth above upon
prior written notification to each of
the Parties hereto.
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2.2
The Parties and Steroid wish to ensure
continuity of supply and orders for the
Product and have agreed to enter into this
Agreement on the terms set out below.
3. This
clause deleted
4. SALE OF
THE PRODUCT
4.1
During the continuance of this Agreement
Steroid shall sell such quantities of
the Product to Stegram and Bioenvision and
Dechra as may be ordered by Stegram
or Bioenvision or Dechra, respectively, at
any time or from time to time.
4.2
Steroid shall not sell any of the Product
to any Person other than the Parties
or their respective Designees or successors
without each Party's prior written
consent and this obligation shall continue
beyond termination of this Agreement.
4.3
Under the terms of this Agreement, from
time to time, Stegram or Bioenvision or
Dechra or Dales shall purchase Product from
Steroid. In the routine operation of
its business and under the terms of this
Agreement, Steroid shall invoice
directly Stegram or Bioenvision or Dechra
or Dales, as the case may be, for
Product delivered to a destination as
directed by each such Party. Title to the
Product shall be taken by Stegram or
Bioenvision or Dechra, or Dales as the case
may be, upon delivery of the Product, with
payment due, in each case, within
sixty (60) days of the date of the related
invoice. The invoice will not be
dated or shipment arranged until Steroid is
notified that the Product is of
acceptable quality.
5. TERMS OF
BUSINESS
5.1
All sales of the Product by Steroid shall
be in accordance with the terms of
this Agreement including, but not limited
to, the Purchase Terms set out in
Schedule 4.
5.2
The Product shall be sold by Steroid
