Clinical Research Services Agreement dated October 24, 2001 w/ amendments 1,2,3



 Exhibit 10.9 
  
 CLINICAL RESEARCH SERVICES AGREEMENT 
  
 This AGREEMENT, entered into as of October 24, 2001, is by and between Clinical Cardiovascular Research, LLC, a limited liability company
established under the laws of the Commonwealth of Virginia, with offices located at Montvale Center, 18310 Montgomery Village Avenue, Suite 620, Gaithersburg, Maryland 20879 (hereinafter referred to as “C2R”), and Cardio Vascular Genetic
Engineering, having its principal place of business at 14272 Franklin Avenue, Suite 110, Tustin, CA 92780 (hereinafter referred to as “Sponsor”). 
  
 WHEREAS, C2R is a clinical research organization dedicated to the clinical development of investigational drugs and devices for cardiovascular indications which provides
sponsors of investigational drugs and devices comprehensive clinical management services, design, implementation, execution and analysis of clinical trials for drugs and devices to treat cardiovascular disorders, access to patients with a variety of
cardiovascular ailments, expert assistance in the medical and commercial evaluation of a product’s profile in selection of an optimum indication, and assistance in the preparation of detailed clinical development plans, regulatory strategies,
and protocols; 
  
 WHEREAS, Sponsor desires to utilize the services of C2R to
assist Sponsor in the clinical development of an investigational drug for cardiovascular indications; 
  
 NOW, THEREFORE, the parties hereto, intending to be legally bound, have entered into this Agreement and do specifically agree as follows: 
  

	1.	RFP RESPONSE, PAYMENT SCHEDULE AND ADDITIONAL STUDIES 

  

	 	1.1	The RFP RESPONSE - CVE 2001 describes the services to be performed hereunder and is attached hereto as Exhibit A (“RFP Response”). C2R will perform services for Sponsor in
connection with the studies (“Study”) referenced in Section E. BUDGET of the RFP Response. The RPF Response describes pricing for the Study and a schedule of specific responsibilities. Exhibit B (“Payment Schedule”) contains the
specific payment schedules for the Study. Exhibit C (“Additional Studies”) contains the conditions under which C2R will be granted rights to conduct additional studies of FGF-1 for Cardio. The RFP Response, Appendix B and Appendix C, which
shall be approved by Sponsor, are deemed part of this Agreement and are incorporated herein by reference; 

  

	 	1.2	Upon signing this agreement, Cardio shall pay C2R a sum of $10,000 to cover the initial filling of the FDA Form 1572. Within 7 days of notification of the FDA that the Study may
proceed, Cardio shall pay C2R the remainder of the prepayment - $154,554.25. 








 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	 	1.3	C2R’s Federal Tax ID # is 541832201. After initial prepayment, payments are to be made net 30 days receipt of invoice to the order of: 

  
 Clinical Cardiovascular Research, LLC 
 Montvale Center 
 18310 Montgomery Village Avenue, Suite 620 
 Gaithersburg, Maryland 20879 
  

	2.	STUDY DEVICE AND MATERIALS 

  

	 	2.1	Sponsor shall provide C2R with copies of the protocol for the Study and such related materials as may be in Sponsor’s possession and necessary to enable C2R to fulfill its
obligations under this Agreement. 

  

	 	2.2	Sponsor shall provide sufficient amounts of all devices, materials, or other substances with which to perform the Study, as well as such sufficient and comprehensive data as may be
required by C2R concerning the stability of the test materials, storage, and safety requirements. 

  

	 	2.3	Sponsor guarantees that no device or test material(s) supplied by Sponsor in connection with the Study or the performance of services is adulterated or mislabeled; and that the
clinical supplies (including any reference products used in the Study) provided by Sponsor are identical in content to the description provided in the Protocol. 

  

	3.	COMPLIANCE WITH GOVERNMENT REGULATIONS 

  

	 	3.1.	C2R will perform the Study in accordance with the Protocol. C2R will also comply in all material respects with all current government regulatory requirements concerning Good
Clinical Practices applicable at the time of study initiation. 

  

	 	3.2.	Should such government regulatory requirements be changed, C2R will make every reasonable effort to satisfy the new requirements. In the event that compliance with such new
regulatory requirements necessitates a change in the Protocol for the Study, C2R will submit to Sponsor a revised Line Item Charge for Sponsor’s acceptance prior to making any changes in the Protocol or Study. 

  

	4.	SPONSOR VISITS TO FACILITIES 

  
 Sponsor’s representatives may visit the Investigational clinics with reasonable frequency, upon reasonable notice, during normal business hours to
observe the progress of the Study, C2R will assist Sponsor in scheduling such visits. 
  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	5.	CONFIDENTIAL INFORMATION / LEGAL PROCEEDINGS 

  

	 	5.1.	C2R shall not disclose or use for any purpose other than performance of the services to be rendered hereunder, Sponsor’s Confidential Information. Both parties to this
Agreement shall hold in confidence the identity of patients and shall comply with the applicable laws regarding confidentiality of patient records. Disclosures to Investigational Review Boards are understood to be required by Law.


  

	 	5.2.	If disclosure of Sponsor’s Confidential Information is required by Law, C2R will promptly notify Sponsor of this requirement and, if possible prior to any disclosure, will
permit Sponsor to oppose such disclosure by appropriate legal action. If C2R, shall be obliged to provide assistance, including testimony or records regarding any Sponsor Study in any legal or administrative proceeding, then Sponsor shall reimburse
C2R its reasonable out-of-pocket costs and its reasonable standard hourly fee for the time expended by its employees or representatives. 

  

	 	5.3.	Sponsor will not disclose to any business or institution not affiliated with Sponsor, without C2R’s written permission, any information pertaining to C2R’s business or
this Agreement, unless such disclosure is required by Law. If such disclosure is required by Law, Sponsor will notify C2R of this requirement promptly, and if possible, prior to any disclosure to permit C2R to oppose such disclosure by appropriate
legal action. 

  

	 	5.4.	Sponsor and C2R acknowledge that any remedy at law for the breach or threatened breach of the Confidential Information provisions of this Agreement may be inadequate to fully and
properly protect the disclosing party and, therefore, the parties agree that the disclosing party may be entitled to injunctive relief in addition to other available remedies; provided, however, that nothing contained herein shall be construed as
prohibiting the disclosing party from pursuing any other remedies available in law or in equity, without limit, for such breach or threatened breach. 

  

	 	5.5.	This Section 5 shall survive the expiration or termination of this Agreement. 

  

	6.	WORK PRODUCT 

  

	 	6.1.	All progress reports will be prepared in C2R’s standard format unless otherwise specified in the Protocol or requested by Sponsor in writing. 

  

	 	6.2.	Raw data in paper, magnetic, or other form will be retained by C2R in compliance with regulatory requirements. Upon expiration of any regulatory requirements to maintain such data
or after ten (10) years, whichever is later, Sponsor shall upon C2R’s request direct that such data be delivered to Sponsor or be retained by C2R. 

  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	7.	TEST ARTICLE 

  
 Upon completion of the Study, unless required by applicable law or regulation and so notified by the Sponsor in writing, any remaining samples of test or
control materials will be returned to Sponsor, at Sponsor’s expense, for retention in compliance with regulatory requirements. If so notified by the Sponsor, C2R will retain samples of test or control materials for a standard storage fee.

  

	8.	INVENTIONS AND PATENTS 

  

	 	8.1.	Any trade secrets or any other information of value relating to the business and/or field of interest of Sponsor or any of its Affiliates including, but not limited to, information
relating to inventions, disclosures, processes, systems, methods, formulae, devices, patents, patent applications, trademarks, intellectual properties, instruments, materials, products, research or development activities and plans, clinical,
preclinical or other data, specifications, computer programs, costs of production, prices or other financial data, volume of sales, promotional methods, marketing plans, strategic plans, lists of names or classes of customers, or lists of suppliers,
that C2R obtains through its consultant capacity with Sponsor during the term of this Agreement, or may have acquired through previous dealings with Sponsor or any of its Affiliates, shall be regarded as held by C2R., in a fiduciary capacity solely
for the benefit of Sponsor, its successors or assigns, and shall not at any time, either during the term of this Agreement, or thereafter, be disclosed, divulged, furnished, or made accessible by C2R to anyone, or be otherwise used by C2R, except in
the regular course of C2R’s providing services for Sponsor under this Agreement. Information shall for purposes of this Agreement be considered to be secret if not known by the public generally, even though such information may have been
disclosed to one or more third parties pursuant to agreements entered into by Sponsor or its Affiliates. 

  

	 	8.2.	Any trade secrets or any other information of value relating to the business and/or field of interest of C2R or any of its Affiliates including, but not limited to, information
relating to inventions, disclosures, processes, systems, methods, formulae, devices, patents, patent applications, trademarks, intellectual properties, instruments, materials, products, research or development activities and plans, clinical,
preclinical or other data, specifications, computer programs, costs of production, prices or other financial data, volume of sales, promotional methods, marketing plans, strategic plans, lists of names or classes of customers, or lists of suppliers,
that Sponsor obtains through its business relationship with C2R during the term of this Agreement, or may have acquired through previous 

  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  
 dealings with C2R or any of its Affiliates, shall be regarded as held by Sponsor in a confidential capacity solely for the benefit of C2R, its successors
or assigns, and shall not at any time, either during the term of this Agreement, or thereafter, be disclosed, divulged, furnished, or made accessible by Sponsor to anyone, or be otherwise used by Sponsor, except in the regular course of Sponsor
receiving services from C2R under this Agreement. Information shall for purposes of this Agreement be considered to be secret if not known by the public generally, even though such information may have been disclosed to one or more third parties
pursuant to agreements entered into by C2R or its Affiliates. 
  

	 	8.3.	C2R shall not divulge any information to Sponsor pursuant to this Agreement that is the proprietary property of a third party. 

  

	 	8.4.	This Section 8 shall survive expiration or termination of this Agreement. 

  

	9.	REMEDIES / INDEMNITIES 

  

	 	9.1.	Should any patient enrolled in the Study suffer any adverse effect directly caused by patient’s participation in the Study, Sponsor will reimburse C2R and/or Study Center for
all hospital and medical costs required for diagnosis and emergency treatment. Further, if any such adverse effect gives rise to a claim against C2R, Sponsor shall indemnify, defend and hold harmless C2R and its officers, medical and professional
staff, employees, and agents and their respective successors, heirs and assigns (the “indemnitees”), against any liability, loss, damage, injury, or expense (including reasonable attorneys’ fees and expenses of litigation) incurred by
or imposed upon the indemnitees or any one of them in connection with any claims, suits, actions, demands or judgments (1) arising out of any theory of product liability (including, but not limited to, actions in the form of tort, warranty, or
strict liability) concerning the Study and related materials or any modification thereof; (2) arising out of any side effect or adverse event, illness or injury resulting from indemnitees’ performance of services for the Study and occurring to
any person involved in the Study; or (3) arising out of damage to any property resulting from and occurring during the indemnittees’ performance of services for the Study. 

  

	 	9.2.	Sponsor’s indemnification under 9.1 (2) and 9.1 (3) hereabove shall not apply to any liability, damage, loss or expense to the extent that it is attributable to the (a)
negligent activities, reckless misconduct or intentional misconduct of the indemnitees; or (b) failure of the indemnitees to adhere to the terms of the Protocol. 

  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	 	9.3.	Sponsor agrees, at its own expense, to provide attorneys reasonably acceptable to C2R to defend against any actions brought or filed against any party indemnified hereunder with
respect to the subject of indemnity contained herein, whether or not such actions are rightfully brought. 

  

	 	9.4.	This Section 9 shall survive expiration or termination of this Agreement. 

  

	10.	INSURANCE 

  

	 	10.1.	Sponsor shall, at its sole cost and expense, procure and maintain comprehensive general liability insurance in amounts not less than $2,000,000 per incident and $2,000,000 annual
aggregate and naming the indemnitees as additional insureds. Such comprehensive general liability insurance shall provide (i) product liability coverage and (ii) broad form contractual liability coverage for the Sponsor’s indemnification under
the preceding section. If Sponsor elects to self-insure all or part of the limits described above (including deductibles or retentions which are in excess of $250,000 annual aggregate) such self-insurance program must be acceptable to C2R and the
C2R insurance carrier. The minimum amounts of insurance coverage required under this section shall not be construed to create a limit of Sponsor’s liability with respect to its indemnification under the preceding section of this Agreement.


  

	 	10.2.	Sponsor shall provide C2R with written evidence of such insurance upon request of C2R. Sponsor shall provide C2R with written notice at least fifteen (15) days prior to the
cancellation, non-renewal or material change in such insurance. 

  

	 	10.3.	Sponsor shall maintain such comprehensive general liability insurance during (i) the continuance of the Study and (ii) a reasonable period after the period referred to in 10.3 (i)
hereabove which in no event shall be less than fifteen (15) years. 

  

	 	10.4.	This Section 10 shall survive expiration or termination of this Agreement. 

  

	11.	LIMITATION OF LIABILITY AND REMEDIES; INDEMNIFICATION 

  

	 	11.1.	THE MAXIMUM AGREED LIABILITY OF C2R SHALL NOT EXCEED THE FEES PAID TO C2R. IN NO EVENT SHALL C2R BE LIABLE TO SPONSOR OR ANY OTHER THIRD PARTY FOR ANY SPECIAL, INDIRECT, EXEMPLARY,
INCIDENTAL OR CONSEQUENTIAL DAMAGES INCLUDING BUT NOT LIMITED TO ANY DAMAGES RESULTING FROM LOSS OF DATA, DELAY IN THE STUDY, LOSS OF PROFITS OR LOSS OF BUSINESS ARISING OUT OF OR IN CONNECTION WITH THIS AGREEMENT OR ANY PRODUCTS, SERVICES OR
MATERIALS FURNISHED HEREUNDER, EVEN IF C2R HAS BEEN ADVISED OR SHOULD KNOW OF THE POSSIBILITY OF SUCH DAMAGES. 

  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	 	11.2.	EXCEPT AS EXPRESSLY STATED TO THE CONTRARY, THE LIMITATION STATED IN SECTION 11.1 SHALL APPLY WHETHER THE ASSERTED CLAIM, LIABILITY OR DAMAGES ARE BASED ON CONTRACT (INCLUDING BUT
NOT LIMITED TO BREACH OR WARRANTY), TORT (INCLUDING BUT NOT LIMITED TO NEGLIGENCE AND STRICT LIABILITY) OR ANY OTHER LEGAL OR EQUITABLE GROUNDS, AND REGARDLESS OF WHETHER THE ASSERTED CLAIM, LIABILITY OR DAMAGES ARISE FROM PERSONAL INJURY, PROPERTY
DAMAGE, ECONOMIC LOSS OR ANY OTHER KIND OR INJURY, LOSS OR DAMAGE. EACH OF SUCH LIMITATIONS IS INTENDED TO BE ENFORCEABLE REGARDLESS OF WHETHER ANY OTHER EXCLUSIVE OR NON-EXCLUSIVE REMEDY UNDER THIS AGREEMENT FAILS OF ITS ESSENTIAL PURPOSE.


  

	 	11.3.	Sponsor acknowledges that the fees set forth in Section E. BUDGET and other economic terms of this Agreement reflect the allocation of risks and the limitations of C2R’s
liability hereunder. 

  

	12.	INDEMNITY FOR SUBCONTRACTOR 

  
 The subcontractors involved in the Study will be indemnified by Sponsor. Sponsor hereby agrees to indemnify the subcontractors, subject to limitations
12.1., 12.2., 12.3., and 12.4, herebelow, from and against any and all loss, cost, damage, claim, or action (including reasonable attorney’s fees) which arise in connection with their involvement with the Study, provided: 
  

	 	12.1.	The conduct of the subcontractor is not negligent, or if negligent, such conduct is not a proximate cause of the loss, cost, damage, claim, or action; 

  

	 	12.2.	Sponsor is properly notified of the claim or lawsuit; 

  

	 	12.3.	Sponsor is given control over the conduct and disposition of the claim or lawsuit; and 

  

	 	12.4.	Sponsor receives the full cooperation of the subcontractor during pendency of the claim or lawsuit. 

  

	13.	FORCE MAJEURE 

  
 Neither party shall be liable for any unforeseeable event beyond its reasonable control not caused by the fault or negligence of such party, which causes
such party to be unable to perform its obligations under this Agreement, and which it has been unable to overcome by the exercise of due diligence. 
  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  
 In the event of the occurrence of such a force majeure event, the party unable to perform shall promptly notify the other party. It shall further use its
best efforts to resume performance as quickly as possible and shall suspend performance only for such period of time as is necessary as a result of the force majeure event. 
  

	14.	ALLOCATION OF RESOURCES 

  
 If delays in performance of the Study are experienced because of Sponsor’s inability to supply C2R with materials or information required to perform
the Study, C2R reserves the right to reallocate resources otherwise reserved for performance of the Study without incurring liability to Sponsor. 
  

	15.	INDEPENDENT CONTRACTOR 

  
 C2R shall act solely as an independent contractor and nothing in this Agreement shall be construed to give C2R the power or authority to act for, bind, or
commit Sponsor. Nothing herein shall be construed to create the relationship of employer and employee, partnership, principal and agent, or joint venture between Sponsor and C2R. 
  

	16.	TERMINATION 

  

	 	16.1.	Sponsor and/or C2R may terminate any Study prior to completion by giving prior written notice if any of the following conditions occur: 

  

	 	16.1.1.	By any party if the authorization and approval to conduct the Study in the United States is withdrawn by the U.S. Food and Drug Administration; 

  

	 	16.1.2.	By Sponsor if animal, human and/or toxicological test results, in the opinion of Sponsor support termination of the Study; 

  

	 	16.1.3.	By Sponsor if the emergence of any adverse reaction or side effect with the Study Drug administered in the Study is of such magnitude or incidence in the opinion of Sponsor to
support termination; 

  

	 	16.1.4.	By Sponsor if Sponsor determines that the results or lack of results obtained from the Study at any given time indicate that the Study is not in accord with Sponsor’s corporate
objectives; 

  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	 	16.1.5.	By Sponsor if Sponsor determines that C2R has failed to abide by or satisfy any of the requirements applicable to the Study and/or contained in this Agreement, or any federal, state
or local laws, regulations or guidelines, or any requirements of the host Institution or facility; 

  

	 	16.1.6.	By C2R if C2R determines that Sponsor has failed to abide by or satisfy any of the requirements applicable to the Study and/or contained in this Agreement, or any federal, state or
local laws, regulations or guidelines, or any requirements of the host Institution or facility; 

  

	 	16.1.7.	By C2R if in C2R’s good faith determination, it is not safe to continue the Study. 

  

	 	16.2.	In the event of termination prior to completion of the Study, Sponsor shall make a final payment for services performed in accordance herewith and terminated pursuant to
sub-paragraphs 17.1.1 through 17.1.8 of this Section and reasonable and non-cancelable obligations incurred through the date of termination. In the event the amount of the advance payment made to C2R is greater than the costs incurred by C2R through
the date of termination, C2R shall reimburse to Sponsor the amount paid in excess by Sponsor. 

  

	 	16.3.	The termination of this Agreement shall not relieve either party of its obligation to the other in respect of (i) maintaining the confidentiality of information, (ii) obtaining
consents for advertising purposes and publication, (iii) indemnification, and (iv) compensation for services performed. 

  

	17.	AMENDMENTS 

  
 No provision of this Agreement, RFP Response, or C2R Payment Schedule may be amended, revoked, or waived except in writing signed and delivered by an authorized officer of each party. Any waiver on the part of either
party of any breach or any right or interest hereunder shall not imply the waiver of any subsequent breach or waiver of any other right or interest. 
  

	18.	VALIDITY AND SEVERABILITY 

  
 If any one or more of the provisions of this Agreement is ruled to be wholly or partly invalid or unenforceable by a court or other government body of
competent jurisdiction then: (a) the validity and enforceability of all provisions of this Agreement not ruled to be invalid or unenforceable shall be unaffected; (b) the effect of the ruling shall be limited to the jurisdiction of the court or
other 
  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  
 government body making the ruling; (c) the provision(s) held wholly or partly invalid or unenforceable shall be deemed amended, and the Court or other government body is authorized to amend and to reform the provision(s) to the minimum
extent necessary to render it valid and enforceable in conformity with the parties’ intent as manifested in this Agreement and a provision having a similar economic effect shall be substituted; and (d) if the ruling and/or the controlling
principle of law or equity leading to the ruling is subsequently overruled, modified, or amended by legislative, judicial, or administrative action, then the provision(s) in question as originally set forth in this Agreement shall be deemed valid
and enforceable to the maximum extent permitted by the new controlling principal of law or equity. 
  

	19.	HEADINGS 

  
 The descriptive headings are inserted for convenience of references only and are not intended to be part of or to affect the meaning of or interpretation of this Agreement. 
  

	20.	ENTIRETY 

  
 This Agreement and the exhibits hereto constitute the entire understanding between the parties with respect to the Scope of Work and supersedes and replaces all previous negotiations, understandings, representations,
writings, and contract provisions and rights relating to the Scope of Work. The parties agree that all services provided hereunder shall be subject to and governed by the terms and provisions set forth herein, and none of the terms and conditions
contained on any proposal, purchase order, invoice, or other writing, shall have any effect or change the provisions of this Agreement except as stated in Section 11 above. If there is any conflict between the terms and conditions of the body of the
Agreement and Exhibits, the terms and conditions contained in the body of this Agreement shall govern. 
  

	21.	NOTICE 

  
 Any notice required or permitted to be given hereunder shall be deemed sufficient if sent by facsimile letter or overnight courier, or delivered by hand to Sponsor or C2R at the respective addresses first given above
or at such other address as either party hereto may designate. If sent by facsimile letter, notice shall be deemed given when the transmission is completed if the sender has a confirmed transmission report. If a confirmed transmission report does
not exist, then the notice will be deemed given when the notice is actually received by the person to whom it is sent. If delivered by overnight courier, notice shall be deemed given when it has been signed for. If delivered by hand, notice shall be
deemed given when received. 
  

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 Clinical Cardiovascular Research, LLC 
 Clinical Research Services Agreement 
  

	22.	GOVERNING LAW 

  
 This Agreement is a Maryland contract. It shall be governed, construed, and interpreted in accordance with the laws of the state of Maryland, without
reference to Maryland’s choice of law or conflict of law provisions or principles. 
  

	23.	ATTORNEY’S FEES 

  
 In the event that Sponsor breaches its obligations or any of its obligations pursuant to this Agreement, C2R shall be entitled to recover, in addition to
any and all other remedies, its reasonable attorney’s fees, expenses, and costs which it incurs in enforcing its rights hereunder. In the event that C2R breaches its obligations or any of its obligations pursuant to this Agreement, Sponsor
shall be entitled to recover, in addition to any and all other remedies, its reasonable attorney’s fees, expenses, and costs which it incurs in enforcing its rights hereunder. 
  

	24.	CONSTRUCTION 

  
 This Agreement shall not be construed more strictly against any party hereto merely by virtue of the fact that the Agreement may have been drafted or
prepared by such party or its counsel, it being recognized that all the parties hereto have contributed substantially and materially to its preparation and that this Agreement has been the subject of negotiations between the parties and is the
product of that negotiation. 
  

	25.	COUNTERPARTS 

  
 This Agreement may be executed in two (2) counterparts, each of which shall be deemed an original and both of which together shall constitute one (1)
instrument. 
  
 IN WITNESS WHEREOF, the parties hereto have entered into this
Agreement to be effective as of the day and year first above written. 
  

							
	 CLINICAL CARDIOVASCULAR
 RESEARCH,
LLC:
	 	Cardio Vascular Genetic Engineering
				
	By	 	 /s/ B.G. White

	 	By	 	 /s/ Jack Jacobs


	 	 	 B.G. White, Ph.D.
 President and Chief Executive
Officer
	 	 	 	Signature
				
	 	 	 	 	 Name
 Title
	 	 JACK JACOBS
 VP & Chief Scientific
Officer

	  
 Date
	 	11/19/01	 	  
 Date
	 	  
 11/17/01

	 	 	 	 	 	 	 

  

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 APPENDIC C – Additional Studies 
  

	1.	C2R shall have the exclusive right to conduct additional clinical studies of FGF-1 provided that C2R has successfully completed all work assigned for Study CVGE-2001-01.


  

	2.	C2R shall provide-Cardio a rebate from the cost of Study 2001-01 in the amount of $50,000 which will deducted from the agreed upon pricing of any future study.









 C2R Line Item Charges 
 Sponsor: 
 Phage Biotechnology Corporation 
  

									
	Protocol: CVGE-2001-01	  	# of Patients:	  	32	  	Est. # CRFs	  	1680
	Drug: FGF-1	  	# of Centers:	  	4	  	Est. Project Duration:	  	26 months

  

							
	 PROJECT INITIATION
	  	 	 	  	 	 
	 Protocol Review and Comment
	  	 	6,400	  	 	 
	 CRF Design
	  	 	5,600	  	 	 
	 Study Reference Manual Development
	  	 	7,800	  	 	 
	 Site Selection & Scientific Presentation
	  	 	8,000	  	 	 
	 CRA/Project Team Training
	  	 	6,920	  	 	 
	 Investigator’s Meeting - Set-up
	  	 	5,300	  	 	 
	 Investigator’s Meeting - Attendance
	  	 	5,920	  	 	 
	 SUBTOTAL
	  	 	 	  	$	48,940
	 STUDY MANAGEMENT
	  	 	 	  	 	 
	 Project Management
	  	 	81,120	  	 	 
	 Clinical Monitoring
	  	 	43,520	  	 	 
	 CLINSight Randomization/Patient Tracking
	  	 	16,000	  	 	 
	 DSMB Meeting Attendance
	  	 	12,800	  	 	 
	 SUBTOTAL
	  	 	 	  	$	153,440
	 MEDICAL MONITORING
	  	 	 	  	 	 
	 Safety Monitoring
	  	$	27,000	  	 	 
	 SUBTOTAL
	  	 	 	  	$	27,000
	 COMPUTER PROGRAMMING & DATA MANAGEMENT
	  	 	 	  	 	 
	 Database Development - Data Entry Screen Design
	  	 	15,000	  	 	 
	 Database Maintenance
	  	 	9,000	  	 	 
	 Edit Specification Development and Programming
	  	 	27,000	  	 	 
	 CRF/DCF Inventory
	  	 	840	  	 	 
	 In-house CRF Review
	  	 	2,520	  	 	 
	 Data Entry & Verification
	  	 	6,720	  	 	 
	 DCF Generation/Resolution
	  	 	1,260	  	 	 
	 Coding - Medication, Adverse Events
	  	 	3,200	  	 	 
	 Database Audit
	  	 	2,520	  	 	 
	 SUBTOTAL
	  	 	 	  	$	68,060
	 MEDICAL WRITING
	  	 	 	  	 	 
	 Integrated Clinical/Biostatistical Report
	  	$	12,000	  	 	 
	 SUBTOTAL
	  	 	 	  	$	12,000
	 BIOSTATISTICS
	  	 	 	  	 	 
	 Develop Report Templates
	  	 	13,500	  	 	 
	 SAS Programming of Tables, Patient Listings, Graphs and Analyses
	  	 	20,000	  	 	 
	 QC of SAS Programming
	  	 	4,500	  	 	 
	 Interim Analyses (DSMB)
	  	 	4,000	  	 	 
	 Final Analysis
	  	 	8,000	  	 	 
	 SUBTOTAL
	  	 	 	  	$	50,000
	 FUNCTIONAL SUPPORT/OVERHEAD
	  	 	 	  	 	 
	 Functional Support
	  	 	132,840	  	 	 
	 Overhead
	  	 	130,455	  	 	 
	 Investigator Contract Negotiation & Payment Processing
	  	 	8,400	  	 	 
	 Systems Support
	  	 	30,079	  	 	 
	 SUBTOTAL
	  	 	 	  	$	301,774
	 	  	 	 	  	
	

	 TOTAL C2R FEES
	  	 	 	  	$	658,214
	 	  	 	 	  	
	


  
 Information
contained in this proposal to C2R. This document and the information contained herein is 
 confidential and must not be disclosed to
third parties without prior written consent from C2R. 







 C2R Line Item Charges 
 Sponsor: 
 Phage Biotechnology Corporation 
  

									
	Protocol: CVGE-2001-01	  	# of Patients:	  	32	  	Est. # CRFs	  	1680
	Drug: FGF-1	  	# of Centers:	  	4	  	Est. Project Duration:	  	26 months

  

							
	 ESTIMATED PASS-THROUGH COSTS
	  	 	 	  	 	 
	 CRF Printing/Binders
	  	$	20,000	  	 	 
	 Site Selection Travel
	  	 	4,000	  	 	 
	 Shipping/FedEx
	  	 	5,760	  	 	 
	 Clinical Monitoring Travel
	  	 	18,000	  	 	 
	 DSMB Meetings
	  	 	24,000	  	 	 
	 Client Meeting Travel
	  	 	12,000	  	 	 
	 SUBTOTAL
	  	 	 	  	$	83,760
	 	  	 	 	  	
	


  
 Information
contained in this proposal to C2R. This document and the information contained herein is 
 confidential and must not be disclosed to
third parties without prior written consent from C2R. 







 C2R Payment Schedule 
 Sponsor: 
 Phage Biotechnology Corporation 
  

									
	Protocol: CVGE-2001-01	  	# of Patients:	  	32	  	Est. # CRFs	  	1680
	Drug: FGF-1	  	# of Centers:	  	4	  	Est. Project Duration:	  	26 months

  

						
	 PROJECT INITIATION
	  	 	  	 	 
	 Protocol Review and Comment
	  	Upon Completion	  	 	 
	 CRF Design
	  	Upon Completion	  	 	 
	 Study Reference Manual Development
	  	Upon Completion	  	 	 
	 Site Selection & Scientific Presentation
	  	Upon Completion	  	 	 
	 CRA/Project Team Training
	  	Upon Completion	  	 	 
	 Investigator’s Meeting - Set-up
	  	Upon Completion	  	 	 
	 Investigator’s Meeting - Attendance
	  	Upon Completion	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 STUDY MANAGEMENT
	  	 	  	 	 
	 Project Management
	  	Monthly (1/26)	  	 	 
	 Clinical Monitoring
	  	Upon Completion	  	 	 
	 CLINSight Randomization/Patient Tracking
	  	Monthly (1/18)	  	 	 
	 DSMB Meeting Attendance
	  	Upon Completion	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 MEDICAL MONITORING
	  	 	  	 	 
	 Safety Monitoring
	  	Monthly (1/18)	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 COMPUTER PROGRAMMING & DATA MANAGEMENT
	  	 	  	 	 
	 Database Development - Data Entry Screen Design
	  	Upon Completion	  	 	 
	 Database Maintenance
	  	Monthly (1/18)	  	 	 
	 Edit Specification Development and Programming
	  	Upon Completion	  	 	 
	 CRF/DCF Inventory
	  	Monthly (1/18)	  	 	 
	 In-house CRF Review
	  	Monthly (1/18)	  	 	 
	 Data Entry & Verification
	  	Monthly (1/18)	  	 	 
	 DCF Generation/Resolution
	  	Monthly (1/18)	  	 	 
	 Coding - Medication, Adverse Events
	  	Monthly (1/18)	  	 	 
	 Database Audit
	  	Upon Completion	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 MEDICAL WRITING
	  	 	  	 	 
	 Integrated Clinical/Biostatistical Report
	  	Upon Completion	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 BIOSTATISTICS
	  	 	  	 	 
	 Develop Report Templates
	  	 	  	 	 
	 SAS Programming of Tables, Patient Listings, Graphs and Analyses
	  	Upon Completion	  	 	 
	 QC of SAS Programming
	  	Upon Completion	  	 	 
	 Interim Analyses (DSMB)
	  	Upon Completion	  	 	 
	 Final Analysis
	  	Upon Completion	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 FUNCTIONAL SUPPORT/OVERHEAD
	  	 	  	 	 
	 Functional Support
	  	Monthly (1/26)	  	 	 
	 Overhead
	  	Monthly (1/26)	  	 	 
	 Investigator Contract Negotiation & Payment Processing
	  	Monthly (1/18)	  	 	 
	 Systems Support
	  	Monthly (1/26)	  	 	 
	 SUBTOTAL
	  	 	  	$	—  
	 	  	 	  	
	

	 TOTAL C2R FEES
	  	 	  	 	 

  
 Information
contained in this proposal to C2R. This document and the information contained herein is 
 confidential and must not be disclosed to
third parties without prior written consent from C2R. 







 AMENDMENT NO. 1 
 TO 
 CLINICAL RESEARCH SERVICES AGREEMENT 
  

			
	Regarding:	 	Amendment to the Clinical Research Services Agreement by and between Clinical CardioVascular Research, LLC and Phage Biotechnology Corporation, Inc dated October 24,
2001.
		
	Studies:	 	CVGE – 2001-01 — FGF –1
		
	Sponsor:	 	 Phage Biotechnology Corporation
 14272
Franklin Avenue, Suite 110
 Tustin, CA 92780


  
 In accordance with the terms and
conditions specified in the Clinical Research Services Agreement dated October 24, 2001 (the “Effective Date”) between Clinical Cardiovascular Research, LLC (“C2R”) and Phage Biotechnology Corporation (“Phage”), and by
mutual agreement of the parties, this Amendment to the Clinical Research Services Agreement is issued. 
  
 The purpose of this Amendment is to provide for additional services under the Clinical Research Services Agreement referenced above. The additional services and budget are described in Exhibit A attached hereto
and incorporated herein by reference. 
  
 Except as provided herein, all other
terms and conditions of the Clinical Research Services Agreement between C2R and Phage dated October 24, 2001 remain unchanged and in full force and effect. 
  
 For Clinical Cardiovascular Research, LLC 
  

			
	 /s/ B.G. White


	 B.G. White, Ph.D.

	 President and Chief Executive Officer

	
	 Date: 10/04/02

	
	 For Phage Biotechnology Corporation

	
	

		
	 Printed name:
  
	 	

	 Title:
  
	 	

	 Date:
  
	 	


  
 [LOGO]








 AMENDMENT NO. 1 
 TO 
 CLINICAL RESEARCH SERVICES AGREEMENT 
  

			
	Regarding:	 	Amendment to the Clinical Research Services Agreement by and between Clinical Cardiovascular Research, LLC and Phage Biotechnology Corporation, Inc dated October 24,
2001.
		
	Studies:	 	CVGE – 2001-01 — FGF –1
		
	Sponsor:	 	 Phage Biotechnology Corporation
 14272
Franklin Avenue, Suite 110
 Tustin, CA 92780


  
 In accordance with the terms and
conditions specified in the Clinical Research Services Agreement dated October 24, 2001 (the “Effective Date”) between Clinical Cardiovascular Research, LLC (“C2R”) and Phage Biotechnology Corporation (“Phage”), and by
mutual agreement of the parties, this Amendment to the Clinical Research Services Agreement is issued. 
  
 The purpose of this Amendment is to provide for additional services under the Clinical Research Services Agreement referenced above. The additional services and budget are described in Exhibit A attached hereto and
incorporated herein by reference. 
  
 Except as provided herein, all other terms
and conditions of the Clinical Research Services Agreement between C2R and Phage dated October 24, 2001 remain unchanged and in full force and effect. 
  
 For Clinical Cardiovascular Research, LLC 
  

			
	 /s/ B.G. White


	 B.G. White, Ph.D.

	 President and Chief Executive Officer

	
	 Date: 10/1/02

	
	 For Phage Biotechnology Corproation

	
	
  

	 Printed name:
  
	 	

	 Title:
  
	 	

	 Date:
  
	 	


  
 [LOGO]








 ATTACHMENT A 
  

			
	 CHANGE

	  	 RATIONAL


	 CRF Design
	  	Ophthalmology CRFs
	 Study Reference Manual Development
	  	Ophthalmology CRFs
	 Site Selection & Scientific Presentation
	  	Visit number Increased from 4 to 8 - final 2 sites to be selected from 6-8 candidates
		
	 Individual Site Training with Dr. Stedman
	  	2 days at 4 centers for Dr. White/ Ms. Riggs
		
	 Project Management
	  	From 2 days/month for Ms. Riggs and COA to 4 days/month for 26 weeks plus 4 days per month for both for the first 13 weeks
		
	 Database Development - Data Entry Screen Design
	  	Ophthalmology CRFs
		
	 Edit Specification Development and Programming
	  	Ophthalmology CRFs
	 CRT/DCF Inventory
	  	Ophthalmology CRFs
	 In-house CRF Review
	  	Ophthalmology CRFs
	 Data Entry & Verification
	  	Ophthalmology CRFs
	 DCF Generation/Resolution
	  	Ophthalmology CRFs








 C2R INVOICE August-September 2002 
  
 CARDIOVASCULAR GENETIC ENGINEERING 
  

									
	 Protocol: CVCE-2001-01
	  	#of Patients:	  	32	  	Est. # CRFs	  	1840
	 . Drug; FCF-1
	  	# of Centers:	  	4	  	Est. Project Duration	  	26 months

  

										
	 	  	BUDGET

	  	CURRENT
CHARGES

	  	 CUMULATIVE
 CHARGES


	 PROJECT INITIATION
	  	 	 	  	 	 	  	 	 
	 Protocol Review and Comment
	  	 	6,400	  	 	0	  	 	6,400
	 CRF Design
	  	 	8,080	  	 	2,020	  	 	8,080
	 Study Reference Manual Development
	  	 	9,720	  	 	2,020	  	 	8,760
	 Site Selection & Scientific Presentation
	  	 	16,000	  	 	4,000	  	 	10,000
	 CRA/Project Team Training
	  	 	6,920	  	 	0	  	 	0
	 Investigator’s Meetings - Set-up
	  	 	5,300	  	 	0	  	 	0
	 Investigators Meetings - Attendance
	  	 	5,920	  	 	0	  	 	0
	 Individual Site Training with Dr. Stedman
	  	 	25,600	  	 	0	  	 	0
	 SUBTOTAL
	  	$	83,940	  	$	8,040	  	$	33,240
	 STUDY MANAGEMENT
	  	 	 	  	 	 	  	 	 
	 Project Management
	  	 	250,052	  	 	27,019	  	 	91,478
	 Clinical Monitoring
	  	 	43,520	  	 	0	  	 	0
	 CLINSight Randomization/Patient Tracking
	  	 	16,000	  	 	0	  	 	0
	 DSMB Meeting Attendance
	  	 	12,800	  	 	0	  	 	0
	 SUBTOTAL
	  	$	322,372	  	$	27,019	  	$	9l,478
	 MEDICAL MONITORING
	  	 	 	  	 	 	  	 	 
	 Safety Monitoring
	  	$	27,000	  	 	0	  	 	0
	 SUBTOTAL
	  	$	27,000	  	$	—  	  	$	—  
	 COMPUTER PROGRAMMING & DATA MANAGEMENT
	  	 	 	  	 	 	  	 	 
	 Database Development - Data Entry Screen Design
	  	 	16,500	  	 	0	  	 	13,000
	 Database Maintenance
	  	 	9,000	  	 	0	  	 	0
	 Edit Specification Development and Programming
	  	 	28,000	  	 	3,000	  	 	12,000
	 CRF/DCF Inventory
	  	 	1,000	  	 	0	  	 	0
	 In-house CRF Review
	  	 	2,760	  	 	0	  	 	0
	 Data Entry & Verification
	  	 	7,360	  	 	0	  	 	0
	 DCF Generation/Resolution
	  	 	1,380	  	 	0	  	 	0
	 Coding - Medication, Adverse Events
	  	 	3,200	  	 	0	  	 	0
	 Database Audit
	  	 	2,520	  	 	0	  	 	0
	 SUBTOTAL
	  	$	71,720	  	$	3,000	  	$	25,000
	 MEDICAL WRITING
	  	 	 	  	 	 	  	 	 
	 Integrated Clinical/Biostatistical Report
	  	$	 12,000	  	 	0	  	 	0
	 SUBTOTAL
	  	$	12,000	  	$	—  	  	$	—  
	 BIOSTATISTICS
	  	 	 	  	 	 	  	 	 
	 Develop Report Templates
	  	 	13,500	  	 	2,500	  	 	10,000
	 SAS Programming of Tables, Patient Listings, Graphs and Analyses
	  	 	20,000	  	 	5,000	  	 	5,000
	 QC of SAS Programming
	  	 	4,500	  	 	0	  	 	0
	 Interim Analyses (DSMB)
	  	 	4,000	  	 	0	  	 	0
	 Final Analysis
	  	 	8,000	  	 	0	  	 	0
	 SUBTOTAL
	  	$	 50,000	  	$	7,500	  	$	15,000
	 FUNCTIONAL, SUPPORT/OVERHEAD
	  	 	 	  	 	 	  	 	 
	 Functional Support
	  	 	132,840	  	 	10,218	  	 	35,764
	 Overhead
	  	 	130,455	  	 	10,035	  	 	35,123
	 Investigator Contract Negotiation & Payment Processing
	  	 	8,400	  	 	2,400	  	 	2,400
	 Systems Support
	  	 	30,079	  	 	2,314	  	 	8,900
	 SUBTOTAL
	  	$	301,774	  	$	24,367	  	$	81,386
	 	  	
	
	  	
	
	  	
	

	 TOTAL C2R FEES
	  	$	868,806	  	$	70,326	  	$	246,104
	 	  	
	
	  	
	
	  	
	


  
 Information
contained in this proposal is proprietary to C2R. This document and the information contained herein is confidential and must not be disclosed to third parties without prior written consent from C2R.







 AMENDMENT NO. 2 
 TO 
 CLINICAL RESEARCH SERVICES AGREEMENT 
  

			
	Regarding:	  	Amendment to the Clinical Research Services Agreement by and between Clinical Cardiovascular Research, LLC and Phage Biotechnology Corporation, Inc dated October 24,
2001.
		
	Studies:	  	CVGE – 2001-01 — FGF – 1
		
	Sponsor:	  	 Phage Biotechnology Corporation
 14272
Franklin Avenue, Suite 110
 Tustin, CA 92780


  
 In accordance with the terms and
conditions specified in the Clinical Research Services Agreement dated October 24, 2001 (the “Effective Date”) between Clinical Cardiovascular Research, LLC (“C2R”) and Phage Biotechnology Corporation (“Phage”), and by
mutual agreement of the parties, this Amendment to the Clinical Research Services Agreement is issued. 
  
 The purpose of this Amendment is to provide for billing by hourly rates for services performed under the Clinical Research Services Agreement referenced above. The 2004 rates are listed in Exhibit A attached
hereto and incorporated herein by reference. 
  
 Except as provided herein, all
other terms and conditions of the Clinical Research Services Agreement between C2R and Phage dated October 24, 2001 remain unchanged and in full force and effect. 
  

	
	For Clinical Cardiovascular Research, LLC
	
	 /s/ B.G. White


	 B.G. White, Ph.D.

	 President and Chief Executive Officer

	
	Date: 3/1/2004

  
 For Phage Biotechnology Corporation

  

			
	 /s/ Jack Jacobs


	 Printed Name :
	 	 JACK JACOBS

	 Title:
	 	 VP & COO

	 Date:
	 	 4/15/04


  
 18310 Montgomery
Village Avenue, Suite 620, Galthersburg, MD 20879 • (301) 208-9100 • Fax (301) 990-9544 







 [LOGO] 
  
 April 13, 2004 
  
 Jack Jacobs, Ph.D. 
 Vice President, Chief Scientific Officer 
 Phage Biotechnology Corp. 
 14272 Franklin Avenue, Suite 110 
 Tustin, CA 92780 
  
 Dear Jack: 
  
 As discussed in Mary’s recent message, we have drafted an amendment to our Research
Agreement to alter the method for calculating your monthly invoice. We are not proposing altering any of the tasks nor how the budgeted task estimates were calculated. The only alteration proposed is the way the tasks are billed. As of January 01,
2004, we have installed an electronic time management system. All of our contracts are being transferred to a uniform hourly billing method. This method allows sponsors, like yourself, to pay for only work/time expended. This is especially important
for trials with slow or erratic enrollment. With the revised system, you only pay for hours utilized not hours projected. 
  
 We had planned to implement the changes with your April 2004 invoice, but once we calculated the March invoice using the old method and the newer approach, there was
actually a substantial reduction in your March invoice. Therefore, we have dated the amendment for March 01, 2004 to effectively save Phage approximately $6000 for the work performed during March 2004. 
  
 If you have any questions please contact me at (301) 208-9100. We look forward to completing
quickly the remainder of group one and reviewing the data with our Data and Safety Team, as well as the FDA. 
  

	
	 Very Best Regards,

	
	 /s/ B.G. White


	 B. G. White, Ph.D.

	 President, CEO


  
 Enclosures (3) 
  







 2004 Hourly Rates 
  

					
	 Senior Consultant - SC
	 	225	 	 
	 Senior Director - Sr Dir
	 	165	 	 
	 Senior Project Manager - SPM
	 	150	 	 
	 Project Manager - PM
	 	135	 	 
	 Clinical Operations Assistant - COA
	 	50	 	 
	 Biostatistics - Bios
	 	125	 	 
	 Safety - RN
	 	100	 	 
	 Finance - ADMN
	 	50	 	 
	 Data Entry - DE
	 	35	 	 
	 Quality Assurance - QA
	 	135	 	 
	 Quality-of-Life - QOL
	 	75	 	 
	Data Management Manager - DIV	 	135	 	 
	 Data Management - DMA
	 	75	 	 
	 Document Control - Doc
	 	50	 	 
	 CRA Manager - CRA Mgr
	 	135	 	 
	 Monitor - CRA
	 	105	 	 
	 Clin Trial Programmer - Prog
	 	100	 	 
	 Pharmacokinetic Consultant - PK
	 	200	 	 
	 Medical Monitor - MD
	 	250	 	 


 Note (1): A twenty percent (20%) overhead charge will
be added to the total of personnel charges. 
 Note (2): All pass-through payments made by C2R will be assessed a 10% service charge Includes - investigator
payments - laboratory payments - printing charges - meeting charges 
 Note (3): Mary Riggs - Sr Dir - B. White - SC 







 AMENDMENT NO. 2 
 TO 
 CLINICAL RESEARCH SERVICES AGREEMENT 
  

			
	Regarding:	  	Amendment to the Clinical Research Services Agreement by and between Clinical
Cardiovascular Research, LLC and Phage Biotechnology Corporation, Inc dated October
24,
2001.
		
	Studies:	  	CVGE – 2001-01 — FGF – 1
		
	Sponsor:	  	 Phage Biotechnology Corporation
 14272
Franklin Avenue, Suite 110
 Tustin, CA 92780


  
 In accordance with the terms and
conditions specified in the Clinical Research Services Agreement dated October 24, 2001 (the “Effective Date”) between Clinical Cardiovascular Research, LLC (“C2R”) and Phage Biotechnology Corporation (“Phage”), and by
mutual agreement of the parties, this Amendment to the Clinical Research Services Agreement is issued. 
  
 The purpose of this Amendment is to provide for billing by hourly rates for services performed under the Clinical Research Services Agreement referenced above. The 2004 rates are listed in Exhibit A attached
hereto and incorporated herein by reference. 
  
 Except as provided herein, all
other terms and conditions of the Clinical Research Services Agreement between C2R and Phage dated October 24, 2001 remain unchanged and in full force and effect. 
  
 For Clinical Cardiovascular Research, LLC 
  

	
	 /s/ B.G. White


	 B.G. White, Ph.D.

	 President and Chief Executive Officer

	
	 Date: March 01, 2004



			
	
	For Phage Biotechnology Corporation
	
	  


	 Printed name:
	 	  


	 Title:
	 	  


	 Date:
	 	  










 EXHIBIT A 
  
 2004 Hourly Rates 
  

			
	 Senior Consultant - SC
	  	225
	 Senior Director - Sr Dir
	  	165
	 Senior Project Manager - SPM
	  	150
	 Project Manager - PM
	  	135
	 Clinical Operations Assistant - COA
	  	50
	 Biostatistics - Bios
	  	125
	 Safety - RN
	  	100
	 Finance - ADMN
	  	50
	 Data Entry - DE
	  	35
	 Quality Assurance - QA
	  	135
	 Quality-of-Life - QOL
	  	75
	 Data Management Manager - DM Mgr
	  	135
	 Data Management - DMA
	  	75
	 Document Control - Doc
	  	50
	 CRA Manager-CRA Mgr
	  	135
	 Monitor - CRA
	  	105
	 ClinTrial Programmer - Prog
	  	100
	 Pharmacokinetic Consultant - PK
	  	200
	 Medical Monitor - MD
	  	250


 Note (1): A twenty percent (20%) overhead charge will
be added to the total of personnel charges. 
 Note (2): All pass-through payments made by C2R will be assessed a ten percent (10%) service charge Includes -
investigator payments - laboratory payments - printing charges - meeting charges 
 Note (3): Mary Riggs - Sr Dir - B. White - SC 
 Note (4): Rates for 2005 will be increased by approximately 5% 







 [LOGO] 
  
 AMENDMENT NO. 3 
 TO 

CLINICAL RESEARCH SERVICES AGREEMENT 
  

			
	Regarding:	  	Amendment to the Clinical Research Services Agreement by and between Clinical Cardiovascular Research, LLC and Phage Biotechnology Corporation, Inc dated October 24, 2001 with subsequent
name change to CardioVascular BioTherapeutics as effected by the May 17, 2004 document.
		
	Studies:	  	Additional Protocol Development – Authorization to begin development on Study 1 – Adjunctive treatment to coronary artery bypass graft (CABG)
		
	Sponsor:	  	 CardioVascular BioTherapeutics
 14272
Franklin Avenue, Suite 110
 Tustin, CA 92780


  
 In accordance with the terms and
conditions specified in the Clinical Research Services Agreement dated October 24, 2001 (the “Effective Date”) between Clinical Cardiovascular Research, LLC (“C2R”) and CardioVascular BioTherapeutics (“Cardio”) formerly
Phage Biotechnology (“Phage”), and by mutual agreement of the parties, this Amendment to the Clinical Research Services Agreement is issued. 
  
 The purpose of this Amendment is to provide for additional protocols to be developed by C2R. Exhibit A attached hereto and incorporated herein by reference lists
in priority order each contemplated protocol. A time and materials estimated budget for the work necessary to develop each protocol is included in Exhibit A. At the sole discretion of Cardio and with written confirmation to C2R, protocols may
be added/deleted or the priority changed. Prior to initiating development on each protocol, Cardio will issue to C2R a written authorization to proceed. Amendment 3, as written, includes authorization to commence protocol development on Study 1 -
Adjunctive treatment to coronary artery bypass graft (CABG). 
  
 Upon completion
of the development of each protocol by C2R and acceptance by Cardio and any consultants of Cardio, C2R will prepare for approval by Cardio an estimated time and materials budget for the conduct of the protocol. An additional amendment to the
Clinical Research Services Agreement, governing the scope of work and budget for each protocol, will be issued for Cardio’s approval. 
  
 Except as provided herein, all other terms and conditions of the Clinical Research Services Agreement between C2R and Phage/Cardio dated October 24, 2001 remain unchanged
and in full force and effect. 
  
 Page 1 of 2 
  
 18310 Montgomery Village Avenue, Suite 620, Galthersburg, MD 20879 •
(301) 208-9100 • Fax (301) 990-9544 







 [LOGO] 
  

			
	For Clinical Cardiovascular Research, LLC
	
	 /s/ B.G. White


	 B.G. White, Ph.D.

	 President and Chief Executive Officer

		
	 Date:
	 	 5-24-04


  

			
	For CardioVascular BioTherapeutics
	
	 /s/ Jack Jacobs


	 Printed name:
	 	 Jack Jacobs

	 Title:
	 	 VP & COO

	 Date:
	 	 5-26-04


  
 Page 2 of 2 

 
 18310 Montgomery Village Avenue, Suite 620, Galthersburg, MD 20879 •
(301) 208-9100 • Fax (301) 990-9544 







 Page 1 of 2 Exhibit A to Amendment 3 
  
 [LOGO] 
  
 EXHIBIT A - AMENDMENT 3 
  
 The proposed protocols are listed below in priority order: 
  
 1. Adjunctive treatment to coronary artery bypass graft (CABG) - The American Heart Association estimates that 519,000 procedures were performed in the US in 2000.
A similar or higher number was performed in Europe. A draft protocol will be completed within thirty days of signature of this letter of intent. An estimated time and materials budget for development of this protocol is - $50,000. 
  
 2. Catheter based delivery of FGF-1. After signing this agreement, C2R will meet with
Cardio’s regulatory and/or clinical cardiology consultant, at a mutually agreeable time, to determine the most efficient way to proceed with a combined biologic/device feasibility trial. In addition, a meeting between C2R and Cardio’s
catheter design and manufacturing partner (Catheter and Disposable Technologies, Inc., Plymouth, MN) may also be requested by Cardio. Once, the regulatory issues have been negotiated with the FDA, C2R will provide protocol(s) drafts within 30 days.
An estimated time and materials budget for development of this protocol is -$75,000. 
  
 3. Peripheral Arterial Disease. The PAD initiative will focus on the assessment of FGF-1 to provide collateralization and/or promote healing and regeneration. Over ten million patients in the US suffer from PAD with an estimated
35,000 limb amputations annually. This initiative initially will focus on developing a working document of the clinical trial methodologies used recently by Genentech, Vascular Genetics, Aventis and Chiron Corporation to study various proteins for
PAD. A plan will be formulated to choose appropriate endpoints for this study, which could include time to healing of both chronic ischemic leg ulcers or diabetic leg ulcers, and more functional endpoints including length of time on a treadmill.
Protocols for these patient populations will be provided within sixty days upon completion of the working document and discussions with Hugh G. Beebe, MD, Director of Clinical Research, The Jobst Vascular Center. An estimated time and materials
budget for development of this protocol is - $110,000. 
  
 4. Wound
Healing/Limb Preservation - It is our plan to initiate discussions with one of the leading centers in the US – the University of Pittsburgh Medical Center, Wound Healing/ Limb Preservation Clinic. This center has conducted clinical
studies of platelet derived growth factor (PDGF), transforming growth factor- beta, platelet derived wound healing formula (PDWHF), and RGD peptide, among others. After discussions with this group, C2R will propose a strategy/protocol to Cardio for
initiation of a study of FGF-1 in this population. An estimated time and materials budget for development of this protocol is - $110,000. 
  
 5. Adjunctive treatment to percutaneous transluminal coronary artery angioplasty (PTCA). The American Heart Association estimates that 1,025,000 angioplasty
procedures were performed in the US in 2000. Of these, 561,000 were PTCA. A draft protocol will be completed within thirty days of completing discussions with interventional cardiologists at the University of Cincinnati and at least two other
locations mutually agreed upon by Cardio and C2R. An estimated time and materials budget for development of this protocol is - $50,000. 
  
 18310 Montgomery Village Avenue, Suite 620, Galthersburg, MD 20879 • (301) 208-9100 • Fax (301) 990-9544 







 Page 2 of 2 Exhibit A to Amendment 3 
  
 [LOGO] 
  
 Stroke – Stroke is the number three killer of Americans and the leading cause of long-term disability. The AHA estimates the prevalence of stroke patients in
the US at 4,800,000. The stoke initiative will be divided into two separate protocols: 
  
 (6). Clotting stokes - Cerebral thrombosis/cerebral embolism. Cerebral thrombosis is the most common stroke. Cerebral emboli are most often caused by clots being discharged from the heart during atrial fibrillation. After discussions
with leading experts, we may further divide this initiative into two groups – (i) adjunctive therapy to acute treatment procedures – carotid endarterectomy and cerebral angioplasty and (ii) treatment of rehabilitating stoke patients.
Protocols for this patient population will be provided within sixty days upon completion of input from stroke opinion leaders(s). An estimated time and materials budget for development of this protocol is - $110,000. 
  
 (7). Ruptured blood vessel strokes – Cerebral hemorrhages/subarachnoid
hemorrhages. These types of stroke are more often associated with early mortality. Further discussions with stroke experts will be needed to plan an initiative in this patient population. An estimated time and materials budget for development of
this protocol is - $70,000. 
  
 18310 Montgomery Village Avenue,
Suite 620, Galthersburg, MD 20879 • (301) 208-9100 • Fax (301) 990-9544