EXHIBIT 10.27
RESEARCH and LICENCE AGREEMENT
(1) BIOENVISION INC.
- and -
(2) VELINDRE NHS TRUST
- and -
(3) UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED
THIS AGREEMENT is made on the 9th day of January 2001
BETWEEN:
(1) VELINDRE NHS HOSPITAL TRUST a specialist cancer hospital whose
address is Velindre Road, Cardiff ("Velindre"); and
(2) UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED a company
incorporated under the laws of England and Wales (company
number 1477909) whose registered office is at 00 Xxxx Xxxxx,
Xxxxxxx XX00 0XX ("Cardiff"); and
(3) BIOENVISION, INC., a company incorporated under the laws of
Delaware, whose registered office is at Xxx Xxxxxxxxxxx Xxxxx,
Xxxxx 0000, Xxx Xxxx, XX 00000 ("Bioenvision")
WHEREAS:
(a) Velindre has intellectual property and know-how related to the
use of l-gossypol and related compounds for the treatment of
human and animal diseases ("Technology"); and
(b) Cardiff is the technology transfer company of Cardiff
University. Cardiff University has assisted in the early stage
development of the Technology; and
(c) Bioenvision is a company engaged in the development and
marketing of medical compounds.
The parties hereby agree to the following terms and conditions
for a licensing agreement for l-gossypol
1 DEFINITIONS
1.1 In this Agreement:
(i) "Velindre" means the Velindre NBS Trust.
(ii) "Trials Unit" means the Clinical Trials Unit at the Velindre
NHS Trust.
(iii) "Trial" means the Phase I study to be performed in cancer
patients at the Trials Unit.
(iv) "Research Period" means the period during which clinical and
pre-clinical studies are conducted with l-gossypol by the
parties to the Agreement.
(v) "Bioenvision" means Bioenvision and includes subsidiary
companies.
(vi) "Technology" means all aspects of the work relating to the
development of l-gossypol and related products.
(vii) "Patents" means patents applied for and patents granted
relating to the composition, manufacture, formulation and or
use of l-gossypol and related compounds.
(viii) "Improvement(s) means any changes or additions to the
intellectual property relating to l-gossypol and related
compounds or products which arise as a result of the Research
done during the Research Period and related to the Technology
and which shall be incorporated into existing patents or new
patents applied for.
(ix) "Product" means a medical compound or compounds developed from
the Technology and designated for sale as a treatment for
human or animal diseases.
(x) "Territory' means Worldwide.
(xi) "Results" means any and all results, data and intellectual
property generated by the Research and clinical studies, and
includes copyright, patents or applications for the same
(protective applications) and similar or related rights.
(xii) "Field" means the use of l-gossypol or related compounds for
the treatment of medical conditions in humans and animals.
1.2 Reference to any statute or statutory provision includes a
reference to that statute or statutory provision as from time
to time amended extended or reenacted.
1.3 Words importing the singular number shall include the plural
and vice versa, words importing the masculine shall include
the feminine and neuter and vice versa, and words importing
persons shall include bodies corporate, unincorporated
associations and partnerships.
1.4 Headings to clauses and paragraphs are for ease of reference
only and shall not affect the interpretation or construction
of this Agreement. The Schedule forms part of this Agreement
and shall be construed accordingly.
2 CONDUCT OF STUDIES AND PAYMENT
2.1 A Phase I clinical study shall be conducted at the Clinical
Trials Unit at Velindre. The study will be performed in cancer
patients and will determine the maximum tolerated dose of
l-gossypol, the side-effect profile and the plasma
concentration of the drug.
2.2 Velindre and the Trials Unit shall use all reasonable
endeavours within the scope of their knowledge and experience
to conduct the Study in accordance with the terms of this
Agreement.
2.3 Velindre will provide Bioenvision with all the scientific
results of the Research on a quarterly basis. A full written
report will reach Bioenvision no later than three (3) months
after the completion of the Phase I Study.
2.4 The Study as described in Schedule 1 (see Clinical trial
Protocol) will be conducted on eighteen (18) patients for a
sum of (pound)48,454.30 exclusive of VAT. Payments by
Bioenvision shall be made to Velindre within thirty (30) days
of receipt of invoices, submitted according to the following
schedule:
Payment 1 (pound)12,000 One month prior to start of Phase I
trial.
Payment 2 (pound)12,000 four months after initial payment.
Payment 3 (pound)12,000 four months after payment 2.
Final payment upon submission of data.
2.5 Bioenvision shall pay directly to sub-contractors for the
preparation, formulation and analysis of plasma concentrations
of l-gossypol.
2.6 Velindre shall supply sufficient racemic gossypol for the
preparation of l-gossypol and shall also perform
pharmacokinetic analysis.
2.7 Bioenvision shall prepare, with the assistance of Velindre,
the CTX for submission to the regulatory authorities.
2.8 If the Phase I clinical trial is completed successfully,
subject to Clause 4.1, Bioenvision agrees to perform further
clinical trials with l-gossypol or related compounds and
Bioenvision agrees to fund these further clinical trials with
l-gossypol or related compounds, subject to agreement of
appropriate budgets. All decisions relating to further
clinical development will be discussed with and approved by
Velindre.
3 CONDUCT OF TRIAL
3.1 During the course of the Trial and during the remainder of the
Research Period, Velindre will answer all reasonable questions
and queries put by Bioerivision concerning the Trial.
3.2 At the end of the Trial period Velindre will supply
Bioenvision with the data and conclusions from the trial and
Bioenvision will provide Velindre with a written report of
its conclusions, including an assessment of market potential
within three (3) months of receiving the data.
4 LICENSING
4.1 Cardiff and Velindre shall grant to Bioenvision an exclusive
worldwide licence to make, have made, use and sell products
based on the Results on the basis that Bioenvision makes
beneficial commercial use of the Results. If, after a period
of three years from the grant of the licence, no commercial
use is made of the Results, Cardiff and Velindre shall have
the right to offer the licence elsewhere. Schedule 2 to this
Agreement sets out the basis for agreement of a licence.
4.2 Neither Cardiff nor Velindre shall enter into discussions or
negotiations with any third party or third parties (other than
Bioenvision) with a view to the grant of a licence to any
third party (whether on an exclusive or non-exclusive basis)
under the Results for the manufacture, use and/or sale of any
products in the Territory.
5 MANUFACTURE AND PRODUCT FORMULATION
Bioenvision shall be responsible for manufacture of l-gossypol
according to standards set down by regulatory authorities for clinical
trials in the UK. A third party may be requested to conduct the
manufacture and formulation of the Product.
6 RESULTS AND IPRs
6.1 Results shall be the property of Cardiff and Velindre.
6.2 The necessity for and timing of any applications for Patents
and/or similar protective applications shall be discussed
between the parties. Protective applications shall be filed by
Bioenvision in the names of Velindre and Cardiff. Bioenvision
shall meet all costs incurred in prosecuting and maintaining
any protective applications.
7 COMMENCEMENT
The Trial shall commence as soon as may reasonably be practicable
following the execution of this Agreement by the parties.
8 CONFIDENTIALITY
8.1 Except as provided in sub-clause 8.4 below, during the term of
this Agreement all Information (howsoever recorded or stored),
which is disclosed by the Discloser to or otherwise comes into
the possession of a Recipient shall be regarded as
confidential and the property of the Discloser and shall not
be disclosed by the Recipient to third parties or used by the
Recipient for any purpose other than stated in this Agreement.
All written Confidential Information shall be marked as such
by the Discloser, and all such information relayed
electronically or verbally shall be reduced to writing within
thirty (30) days.
8.2 The Recipient shall be responsible and liable to the Discloser
for any non-observance or breach of the terms of
confidentiality herein contained by its or their employees.
Each party shall restrict disclosure of Information to its
employees having a need to know such Information for the
purposes of the performance of their obligations and
responsibilities hereunder.
8.3 The obligations governing confidentiality and/or use contained
in this Clause 8 shall continue for the term of this Agreement
and for ten (10) years thereafter.
8.4 The provisions governing confidentiality and/or non-use
contained in sub-clause 8.1 above and sub-clause 8.6 below
shall not apply to any part of the Information which the
Recipient is able to demonstrate:
(i) was lawfully in the Recipient's possession and known
to it prior to disclosure or receipt thereof; or
(ii) was in the public domain or the subject of public
knowledge at the time of disclosure to or receipt
thereof by the Recipient; or
(iii) becomes part of the public domain or the subject of
public knowledge after the date of disclosure to or
receipt thereof by the Recipient but through no fault
of the Recipient; or
(iv) becomes available to the Recipient from a third
party not in breach of legal obligation of
confidentiality to any of the parties hereto in
respect thereof; or
(v) is required to be disclosed by law or by order of any
court of competent jurisdiction or by order of any
regulatory authority.
8.5 Cardiff and Velindre further undertake that any reports
produced by Bioenvision under the terms of this Agreement
shall not be disclosed to third parties unless agreed in
writing by Bioenvision.
8.6 Results shall not be disclosed to third parties by the parties
hereto during the Research Period.
9 PUBLICATION
Bioenvision recognizes that Cardiff and Velindre shall seek to publish
details of the work that is the subject of this Agreement and any
resulting patents subsequent to filing any relevant patent
applications. Bioenvision agrees that Cardiff and Velindre shall be
permitted to present at symposia, international, national, or regional
professional meetings, and to publish in journals, theses,
dissertations or otherwise of their own choosing, details of the work
and any such patents, provided, however, that Cardiff and Velindre
shall discuss any such publication or presentation with Bioenvision,
and Bioenvision shall have been furnished copies of any proposed
publication or presentation at least two (2) months in advance of the
submission of such proposed publication or presentation to a journal,
editor, or other third party. Bioenvision shall have two (2) months,
after receipt of said copies, to object to such proposed presentation
or proposed publication because there is further patentable subject
matter which needs protection. In the event that Bioenvision makes such
objection, said researcher(s) shall refrain from making such
publication or presentation for a maximum of six (6) months from date
of receipt of such objection in order for Cardiff and Velindre to file
UK and/or other patent application(s) directed to the patentable
subject matter contained in the proposed publication or presentation.
10 TERM & TERMINATION
10.1 This Agreement shall commence on the Effective Date and shall
(subject as otherwise provided elsewhere in this Agreement)
remain in force until the end of the Trial period or the end
of any further option period, as described in Clause 4.1
PROVIDED THAT any party ("the Terminating party") shall have
the right to terminate this Agreement by notice in writing to
the other parties upon the happening of any of the following
events:-
10.1.1 if any other party ("the Defaulting party") is guilty
of any breach nonobservance or non performance of any
of its obligations hereunder and does not remedy the
same (if capable of remedy) within thirty days of
written notice of such failure or breach being given
by the Terminating party; or
10.1.2 if the Defaulting party ceases to carry on business
or is unable to pay its debts in the ordinary course
of business or enters into liquidation or analogous
proceeding in any jurisdiction outside the United
Kingdom (other than for the purpose of a solvent
reconstruction or amalgamation) or has a receiver,
administrator or administrative receiver (or
analogous person in any jurisdiction outside the
United Kingdom) appointed over the whole or any part
of its assets; or
10.1.3 if; before the end of the Clinical Trial Period,
Bioenvision shall judge that the results of its
evaluation indicate that the outcome will be of no
commercial benefit to Bioenvision, the Agreement may
be terminated, subject to Bioenvision paying all
sums and for all uncancellable commitments to which
Velindre is obligated for the work.
10.1.4 Bioenvision shall have the right to terminate the
Agreement without the need to pay for the clinical
trials if the Phase I or the Phase II trials fail to
receive ethical approval.
10.2 Upon termination of this Agreement for whatever reason:-
10.2.1 (save for any claim in respect of lack of good faith
and/or failure to enter into negotiation as required
herein) no party shall have any claim against the
other by reason only of failure by the parties to
agree the terms of any licence as referred to in
Clause 4.
10.2.2 Cardiff and Velindre shall as soon as practicable
after termination of this Agreement either destroy or
return (at Bioenvision's option) all of Bioenvision's
Confidential Information (save for reports as defined
in Clause 3.2 hereof), and all copies and extracts
thereof in its possession and shall certify in
writing to Bioenvision that all such information has
been destroyed or returned as the case may be.
10.2.3 Bioenvision shall as soon as practicable after
termination of this Agreement either destroy or
return (at Cardiff and Ve1indre's option) all of
Cardiff and Velindre's Confidential Information (save
for the report as defined in Clause 2.3 hereof) and
all copies and extracts thereof in its possession and
shall certify in writing to the other parties that
all such information has been destroyed or returned
as the case may be.
10.3 The termination of this Agreement for any reason shall be
without prejudice to the rights and obligations of the parties
thereunder accruing up to and including the date of such
termination. Clause 8 shall continue notwithstanding
termination of this Agreement.
11 FORCE MAJEURE
No party hereto shall be liable nor deemed to be liable to any other
party for failure or delay in meeting any obligation hereunder due to
strikes or lockouts (whether of their own employees or those of others)
acts of God, warfare, flood, acts of government or governmental agency
or any other cause beyond the control of the party which had a duty to
perform.
12 SEVERABILITY
If any provision of this Agreement is found by any court or
administrative body of competent jurisdiction to be invalid or
unenforceable the invalidity or unenforceability of such provision
shall not affect the other provisions of this Agreement and all
provisions not affected by such invalidity or unenforceability shall
remain in full force and effect unless severance of the invalid or
unenforceable provision would reasonably frustrate the commercial
purposes of this Agreement. The parties hereby agree to attempt to
substitute for any invalid or unenforceable provision a valid or
enforceable provision which achieves to the greatest extent possible
the economic objectives of the invalid or unenforceable provision
without itself being invalid or unenforceable.
13 ASSIGNMENT
This Agreement shall be binding upon and inure for the benefit of the
successors of the parties hereto. Save as provided herein neither party
shall have the right to assign this Agreement or any rights under it to
any third party without the prior written consent of the other party.
14 WAIVER
The waiver by any party of a breach or default of any of the provisions
of this Agreement by any other party shall not be construed as a waiver
of any succeeding breach of the same or other provisions nor shall any
delay or omission on the part of any party to exercise or avail itself
of any right power or privilege that it has or may have hereunder
operate as waiver of any breach or default by any other parry.
15 NOTICE
Any notice, consent or other communication authorised or required to be
given hereunder or for the purposes hereof may be served by any party
on the other and shall be in writing and sent by personal
" delivery or by recorded delivery or registered post or fax, in the case
of personal delivery or post to the addresses of the parties set out
above or to such other address as may have been notified by any party
as their address for service and in the case of fax, to the following
numbers or to such other number as may have been given by any party as
its fax number for service:
Cardiff: (0) 44 29 20874189
Velindre: (0) 00 00 00000000
Bioenvision: (0) 00 000 000 0000
Any notice sent by post shall be deemed to have been served five (5)
days after the time that the same shall have been posted. Any notice
served by fax shall be deemed to have been served twenty-four hours
after transmission.
16 ENTIRE AGREEMENT
This Agreement constitutes the entire and only Agreement between the
parties hereto relating to the subject matter hereof and overrides and
supersedes any prior arrangements or oral discussion between the
parties.
17 NO PARTNERSHIP
Nothing in this Agreement shall create a partnership or joint venture
between the parties hereto each of whom acts as an independent
principal and not as the agent or partner of the other and no party
shall have any authority to enter into any engagements or make any
representation or warranty on behalf of or pledge the credit of or
otherwise bind or oblige the other party hereto.
18 ANNOUNCEMENTS
Save as required by law or by competent regulatory authority no party
shall make any public announcements as to the existence of this
Agreement or as to its contents without the prior written consent of
the other parties such consent not to be unreasonably withheld.
19 LAW
This Agreement and the rights and duties of the parties hereunder shall
be governed by and construed in accordance with English law and the
parties hereby submit to the exclusive jurisdiction of the English
Courts in all matters relating hereto.
19 MISCELLANEOUS
19.1 This Agreement may not be amended, supplemented or otherwise
modified except by an instrument in writing executed by all
parties hereto with the same formality as this Agreement is
executed.
19.2 Each party hereto shall be responsible for the payment of its
own costs (and not those of the other party) in connection
with the negotiation preparation and execution hereof.
19.3 Each party hereto represents and warrants to the other that
the signatories hereto for and on behalf of that party have
been fully empowered to execute this Agreement on its behalf
and that all necessary action has been taken and all
requisite approvals have been obtained to authorize such
execution.
19.4 All sums expressed in this Agreement or otherwise payable in
accordance with the terms of this Agreement are expressed
exclusive of VAT which shall (if due) be payable in addition
at the applicable rate from time to time.
IN WITNESS whereof the parties hereto have executed and delivered this Agreement
as a Deed the day and year first above written.
for and on behalf of Velindre NHS Trust
Signed by /s/
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In the presence of: /s/
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for and on behalf of Bioenvision
Signed by /s/
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in the presence of: /s/
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for and on behalf of University Collage Cardiff Consultants Limited N.B.B. in
the presence of:-
Signed by /s/
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in the presence of: /s/
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SCHEDULE I - Heads of Terms for Licence Agreement
1. Field Human and animal disease
2. Patents/Results, as defined in the Agreement
3. Territory Worldwide
4. Licensors UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED
and
VELINDRE NHS TRUST
5. Licensee BIOENVISION INC.
Licensee to be permitted to grant sub-licences at its discretion ("provided that
all sub-licences terminate automatically upon termination of the head licence")
- Bioenvision shall ensure that sub-licencees shall abide by the terms of
the Agreement.
- Cardiff and Velindre to be promptly notified of any sublicence granted
by Bioenvision
- Licensee to use all reasonable endeavours to exploit the
Results/patent(s)
- Licensee to pay Licensors 25% of its net receipts arising from any
sub-licence (net of Licensee's development costs to date and costs in
entering into sub-licence) granted prior to completion of Phase II
trials in cancer. Licensee to pay Licensors 15% of its net receipts
arising from any sub-licence (net of Licensee's development costs to
date and costs in entering into sub-licence) granted after completion
of Phase II trials in cancer and prior to submission of an NDA or
corresponding Product Licence application in a European country.
6. Prosecution -Licensee to be responsible for the prosecution and
maintenance of any relevant Patents at Licensee's
cost.
-Licensee to have the express right to take action
against infringers of any Patents and/or "passers
off" in the name of and with the assistance of the
Licensors but at the cost of Licensee; in the event
that Licensee recovers any damages/awards such will
belong to Licensee.
7. Option -Licensee to have "first option" over any Patent(s)
in the event that the Licensors wish to assign or
transfer such patent(s).
8. Improvements -Licensors to notify Licensee of any and all
improvements; incremental improvements to be
available as of right to Bioenvision at no extra
charge beyond existing royalty.
9. Products -Licensee to bear product liability risk and
indemnify Licensors against any third party product
liability claims for damage/personal injury.
-Licensors to indemnify Licensee against claims that
any patent and/or party intellectual property or
other rights.
10. Royalties a rate of 2.5% on net sales of Products by
Bioenvision on sales up to $50m per year, Velindre
will receive 2% and Cardiff will receive 0.5%, this
will rise to 3% on those sales over $50m per year,
Velindre to receive 2.5% and Cardiff will receive
0.5%.
Licensors to have right of access to Licensee's
records to verity "net sales value".
11. Term Licence to continue for the lifetime of any patents
filed pursuant to this Agreement or for 10 years,
whichever is the longer. Licensee to have the right
to surrender its licence back to Licensors without
penalty at any time on not less than 3 months notice.
12. Indemnity Bioenvision will obtain and fund patient indemnity
for a fixed term (18 months) during the Phase I
clinical trial. Additional patient indemnity
insurance will be obtained and funded by Bioenvision
if a Phase II trial is agreed by the parties
according to Clause 2.6.
