. December 2, 2004 Mary J. Gibson University of California, Lo$ Angeles Office of Contracts & Grants Administration 10920 WJI$hire Blvd. Suite 1200 Los Angeles, CA 90024 Re: Amendmer'lt No.1 -- Subject to the full execution of this letter Amendment, the parties hereby amend the Clinical Trial Agreement (the" Agreement" ) between The Regents of the University of California, on behalf of its Los Angeles campus, (" Institution" ) and Berfex, Inc., formerly Berlex Laboratorie~, Inc., (" Sponsor" ) for the conduct of a clinical research study in accordance with Protocol Number 305405 entitled;" Study Of The Safety, Tolerability And Efficacy Of Spheraminel8> Implanted Bilaterally Into The Postcommissural Putamen Of Patients With Advanced Parkin$on' s Disease" ,which was fully executed on February 3, 2004. Paragraph two of the preamble on page 1 of the Agreement $hall be replaced in its entirety a$ follows: WHER~AS: Institution under this Agreement with Sponsor, IS willing to perform work specific 10 the neurological scope of work in accordance with ProtoCOl Number 305405 (under the direction of Dr. Jeff Bron$tein). in which Study Subjects enrolled by UCLA will be transported to certain neurosurgical treatment center$ with $pecial expertise in stereotactic surgery. designated by Sponsor, and return to UCLA for follow-up care; and Sponsor will enter into $ole and separate agreements with $aid neurosurgical treatment centers for the performance of said neurological and neurosurgical work as rnentioned- above and in accordance with Protocol Number 305405. All other terms and conditions of the Agreement shall remain in full force and effect, If the foregoing terms and conditions are acceptable, please have an authorized representative of at' ;/ P ;J..(' ar: (l./
Transcript
31020838:e-"
04i23/2007 OCTAGON RISK 02/2413:17 PAGE
.
December 2, 2004
Mary J. Gibson
University of California, Lo$ Angeles
Office of Contracts & Grants Administration
10920 WJI$hire Blvd. Suite 1200
Los Angeles, CA 90024
Re: Amendmer'lt No.1--
Subject to the full execution of this letter Amendment, the parties hereby amend the Clinical Trial
Agreement (the" Agreement" ) between The Regents of the University of California, on behalf
of its Los Angeles campus, (" Institution" ) and Berfex, Inc., formerly Berlex Laboratorie~, Inc.,
(" Sponsor" ) for the conduct of a clinical research study in accordance with Protocol Number
305405 entitled;" Study Of The Safety, Tolerability And Efficacy Of Spheraminel8> Implanted
Bilaterally Into The Postcommissural Putamen Of Patients With Advanced Parkin$on' s
Disease" ,which was fully executed on February 3, 2004.
Paragraph two of the preamble on page 1 of the Agreement $hall be replaced in its entirety a$
follows:
WHER~AS:
Institution under this Agreement with Sponsor, IS willing to perform work specific 10 the
neurological scope of work in accordance with ProtoCOl Number 305405 (under the
direction of Dr. Jeff Bron$tein). in which Study Subjects enrolled by UCLA will be
transported to certain neurosurgical treatment center$ with $pecial expertise in
stereotactic surgery. designated by Sponsor, and return to UCLA for follow-up care; and
Sponsor will enter into $ole and separate agreements with $aid neurosurgical treatment
centers for the performance of said neurological and neurosurgical work as rnentioned-
above and in accordance with Protocol Number 305405.
All other terms and conditions of the Agreement shall remain in full force and effect, If the
foregoing terms and conditions are acceptable, please have an authorized representative of
at' ;/ P;J..(' ar: (l./
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In$titution sign and date both originals of this Letter Amendment No.1, and return both original
Thank you in advance for your kind cooperation.
Very truly yours.
Signature: :~,k~~~~-
Name: J S~-Mr-~u._~~.):k.J. 6t..MiXi..lIC.JD~&- J. ..'
TItle: ~~~:;;g I~~~t'jj?;~~~'
Date: ?t!:>:J' L'-'"1A4 0 r
Agreed and Accepted by The Regents of The University
of California, on behalf of its Los Angeles campus:
~Signature: ..;~.(\\ ==~", .Name: Jeff 'Bro~tein. ~~O. ..'\ C.-!D~te: -L~ v ~" .:: ..'
J
#/ /fl.I;): ~.er'
documents to: INC Research, Inc. (Contract Research Organization)
Attention: General Counsel
4700 Falls of Neuse Road, Suite 400
Raleigh, North Carolina 27609-6200
31020838~PAGE 04/24OCTAGON RISK13:17 804/23/2007
CUNICAL TRIAL AGREEMENT
PROTOCOL NUMBER 305405
PROTOCOL TITLE: "Study of the safety, tolerability and efficacy of Spheramine@implanted bilaterally into the postcommissural putamen ofpatients with advanced Parkinson's disease"
THIS AGREEMENT is entered into by and between BERLEX LABORATORIES. a division ofBerlex Laboratories, Inc., with its office and place of busines$ at 2600 Hilltop Drive,P.O. Box 4099, Richmond, CA 94806 ("Spo/lsor") and The Regents of the University ofCalifornia on behalf of its Los Angeles campus with the office and place of business at 10920Wilshire Blvd., Ste. 1200, Los Angeles, CA 90024-1406 ("Institution").
WHEREAS:
Institution under this Agreement with Sponsor, is willing to perform work specific to theneurological scope of work in accordance with Protocol Number 305405 (under the direction ofDr. Jeff Bronstein), in which Study Subjects enrolled by UCLA will be transported to StanfordUniversity for neurosurgIcal treatment, and return to UCLA for follow~up care; and Sponsor willenter into a sole and separate agreement with Stanford University to perform said neurologicaland neurosurgical work 8S mentioned-above and in accordance with Protocol Number 305405.
NOW THEREFORE: In consideration of the mutua] covenants, promises and undertakingsprovided herein and other good and valuable consideration, the receipt and sufficiency of whichare hereby acknowledged, Sponsor and Institution agree as follows:
Protocol
The clinical research study ("Study") shall be performed by the Institution under thedirection of and Jeff Bronstein, M.D. ("Jnvestigator") in accordance with Protocol number305405 UStudy of the safety, tolercability and efficacy of Spheramine@ implantedbilaterally into the postcommissuraj" putamen of paiients with advanced Parkinson'sdisease" ("Protocol"), a copy of which is attached to this Agreement as Exhibit A. All theterms of Exhibit A are incorporated and made a part of this Agreement. Any change,amendments or modifications to the Protocol or this Agreement must be authorized inwriting by Berlex and Institution, including, but not limited to increase in payment for theStudy. The Study shalJ be under the direction of the Investigator, provided, however inthe event that the Investigator leaves the Institution or otherwise terminates his or herinvolvement in this Study, Institution shall have the right to designate anotherinvestigator to continue the Study, subject to approval by the Sponsor, which approvalshall not be unreasonably withheld- The Investigator shall determine the manner ofperformance of the Study in accordance with his or her clinical judgment, provided,however that the Investigator may not deviate from specific procedures outlined in theProtocol. Institution and the Investigator shall comply with all federal, state andmunicipal laws and guidelines concerning human research applicable to the Protocol.Any Amendment to a Protocol signed by the Investigator and Sponsor will be consideredan approv~d "Protocol Amendment." "
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2. Payment
The payments will beadjusted on a pro rata basis for the actual number of subjects entered in the Study andfor whom completed Case Report ForTn$ have been accepted by Sponsor.
Reporting3,
Sponsor shall have access to all laboratory and clinical data generated pursuant to theProtocol at times mutually agreed upon by the parties and during normal business hours;provided, however, that Institution and Investigator shall not disclose to Sponsor, exceptas necessary. any confidential information regarding patients, including, but not limited to,the identify of research subjects, their medical records and other related confidentialmedical information. Institution shall provide Sponsor with originals of Case ReportForms on an ongoing basis. The Institution and the Investigator shall, during andfollowing completion of the Study. provide the FDA access to inspect and audit CaseReport Forms. laboratory and clinical data generated pursuant to the Protocol. and alldata, information and procedures relating to the conduct of the Study, as provided by
applicable law.
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Terms of the Agreement4.It is agreed that the clinical Study subject to this Agreement will be initiated on or aboutJanuary 2003, and end September 2006. It Is expected that the Investigator will enrollup to a total of 10 subjects during a 6-month enrollment period and that the Investigator'sparticipatIon in the study will not exceed 40 months. When the total number ofcompleted evaluable patients has been achieved in the Study as a whole, enrollment ofnew subjects by the Investigator will terminate upon written notification by the Sponsor-Institution shall provide Sponsor written evidence of approval by the InstitutionalReview Board (IRB) of the Study and Informed Consent documents. prior to the Sponsor
authorizing the initiation of the Study.
Confidential Information5.j~
Ij
iJji
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All information provided by Sponsor during the course of the Study. that is, by industrystandards. treated as confidential and proprietary, including such wrJtten information aspreclinical data or such information that is orally conveyed confidentially, and confirmedto be confidential, in writing, within twenty (20) days of oral disclosure will be keptconfidential and disclosed only to the clinical personnel involved in conducting the Study("Confidential Information"). The Protocol and related documentation may be provided inconfidence to the appropriate IRB. Confidential Information does not include information
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6. Publication
Institution and the Investigator shall have the light to publish or publicly presentinformation developed by Institution pursuant to performance of the Study subject to thefollowing limitations:
a. Institution and Investigator shall provide Sponsor with an advance copy of anyproposed publication or oral presentation at least thirty (30) days prior to the dateof the planned submission or presentation and Sponsor shall have thirty (30)days to recommend any changes it reasonably believes are necessary topreserve the confidentiality of Sponsor's Confidential Information. Institution andInvestigator shall delete such Confidential Information; and
b. If Sponsor informs Institution, within thirty (30) days of receipt, of an advancecopy of any proposed publication or oral presentation that such publication orpresentation could be expected to have a material adverse effect on Sponsor'sability to obtain patents on any inventions described in the publication orpresentation, Institution and Investigator shall delay or prevent such publicationor presentation for a period of forty-five (45) days to permit the filing of anydesired patent application.
In the case of a multicenter study, the Institution and Investigator will publish the resultsof this study cooperatively and not prior to publication of the results of the multicenterstudy, except that Institution shall have the right to publish the results following thecooperative publication or twelve (12) months following the close of the Study, whicheveroccurs first.
7- Publicity
Neither' Party shall engage in advertising or promotional or fundraising activities,including press interviews, related to the subject matter of this Agr'eement without theprior written consent of the other Party. No party to this Agreement shall. without the
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prior written approval of the other party, use the name of such party or any of itsemployees in connection with any press release, advertising, promotional literature, orany other publicity matters.
8. Inventions
The Institution will disclose promptly to Sponsor any and all inventions and discoverieswhich are conceived and reduced to practice in the direct performance of the Protocol("collectively "Inventions"). All Inventions which necessarily use and necessarilyIncorporate the Study Material provided by Sponsor shall be the sole property ofSponsor. Institution will execute any and air documents or other instruments, reasonablynecessary to apply for and obtain patent{s) for such Inventions. All such Inventions andpatents shall be the exclusive properly of Sponsor. These obligations shall continuebeyond the termination of this Agreement.
9.
10-
a.
b.
iWhenever the Institution or the Investigator has information from which it may ressonablybe concluded that anhas occurred.
ii!
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The Sponsor agrees to provide a defense against any claims brought or actions filedagainst the Investigator, the Institution and/or other affilieted hospitals involved m Protocolactivities covered by this Agreement. their trustees, officers, agents, employees, students,
which are ,,
~,j
Neither the Institution, the Investigator, nor any other indemnitee shall compromise or settleany claim or action which involves the indemnity herein without the prior written 6pprov61 ofthe Sponsor. The Sponsor shall, not settle or compromise any claim or action whichinvolves the indemnity herein that admits the fault or liability of Institution, Investigator orother indemnitee, without the prior written consent of the Institution, such consent not to be
unreasonably withheld.
I ermination/Surviva I11.This Agreement shall be subject to termination by the Sponsor upon (30) days prior writtennotice to the Institution and Investigator. Institution may terminate the Study upon written noticeto the Sponsor if (1) in the best medical judgment of the Principal Investigator continuation ofthe Study will result in a safety risk to the subjects, or (2) the FDA or IRS approval has beenrevoked. If the Study is terminated before its completion, <ill costs incurred by Institution in theconduct of the study, including uncancellable commitments undertaken up to the point oftermination will be reimbursed by Sponsor- The smount of this final payment will include thecosts incurred for each patient not completing the full course of the study at the time it isterminated. The parties will safely withdraw subjects from the Study over a mutually agreeableperiod if thirty (30) days notice is insufficient, bssed upon evaluation of risks to subjects. Anyfunds paid in advance will be prorated and any exce5S funds will be returned to Sponsor. If this
Study is termin<ited before completion, the Investigator will furnish an acceptable Investigator'sFinal Report to Sponsor. and will cooperate fully in providing completed Case Report Forms and
access to appropriate records.
The provisions of Sections 3,5, 6, 7,8,9, 10, 11 and 12 will survive expiration or
termin6tion of this Agreement.
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Representations12.
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13. Conflict of Interest
The investigator acknowledges that there is no conflict of interest between him andSponsor which would inhibit or affect performance of the work specified in thisAgreement; no collateral benefit has been offered for participating in the Agreement,such as promises of gifts, future employment, or trovel that is not related to theAgreement; and no gifts or other benefits have been offered to any family members. It isfurther certified that he/she wilj promptJy advise Sponsor in the event any conflict ofinterest arises during the tellil of this Agreement.
14. Debarment Provision
The Institution: (a) certifies that neither Institution or any employee who will beperforming work on this Study, on behalf of InstJtution is currently debarred by the FDAOr other U.S. regulatory body; (b) agrees that it will promptly notify Sponsor in the eventof any such debarment, conviction, threat or indictment occurring during the term of thisAgreement or one (1) year following its termination or expiration; and (c) agrees not toempJoy any person in connection with any of the work to be performed under thisAgreement who has been debarred or convicted of a crime for which a person can bedebarred under 21 CFR 335(a).
15. Notice
AI! notices to be given as required in this Agreement shall be in writing and shall bedelivered personally, sent by facsimile, telegram or mailed to the parties at theaddresses set forth below, Or such otller addresses as the parties may designate inwriting.
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To Sponsor: 8erfex LQboratories2600 Hilltop DriveP.O. Box 4099Richmond, CA 94806Attn: ClinicaJ Operations with a copy to Legal Dept.
To Institution: The Regents of the University of California10920 Wilshire Blvd., Ste. 1200Los Angeles, CA 90024-1406Attn: Industry Contract Officer
16. Miscellaneous
This Agreement sets fortJ1 the entire agreement between the parties with respect to thesubject matter hereof. The invalidity or unenforceability of any ter'm or provision hereof
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This Agreement shall be binding upon and inure to the benefit of each of the partieshereto and their successors arid permitted assigrls; provided, however, this Agreementmay not be assigned by any party without the prior written approval of the other parties,except Sponsor may transfer Or assign its rights and obligations under this Agreement toa party which acquires the business of Sponsor to which this Agreement relates throughmerger, sale of a~sets or otherwise. This Agreement may not be modified or amendedexcept by an instrument duly signed by the partIes. This Agreement shall be governedby the laws of the State of California.
TITLE: "Study of the safety, tolerability and efficacy of Spheramine@implanted bilaterally into the postcommissural putamen. of patientswith advanced Parkinson's disease"
PROTOCOL ATTACHED
Protocol #305405Clinical Trial Agreement
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"
Exhibit B
audaet and Payment Schedule
8erlex Laboratories agrees to pay all payments required under this Agreement as outlinedbelow. The Institution wi I! provide necessary information to Berlex; including name and addressof payee and Federal Tax Identification number. Bet1ex will pay up to $34,790.00 for eachevaluable patient that fully completes the protocol requirements and for whom a completedCase Report Form (CRF) is received. All payments are processed within thirty (30) days ofreceipt of the completed Case Report Form(s).
Grant payments will be made as follows:
-
r4"615
The paYment for CI patient at any given study visit is as follows:
