ALLPHASE

    Clinical
Research

    


    YM
BIOSCIENCES INC.

    


    PROPOSAL
SUMMARY PR1

    (Detailed)

    


    Palliative
Radiotherapy

    


    A
Phase I-II clinical study of Nimotuzumab (TheraCIM-h-R3) in

    combination
with external radiotherapy in stage IIb, III, IV NSCLC.

    (Phase
II Portion only)

    


    December
16th,
2008

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    1.
Proposal Details

    


    
      
        
          
            
              	
                      Title:

                    	
                      A
      Phase I-II clinical study of Nimotuzumab (TheraCIM-h-R3) in combination
      with external radiotherapy in stage IIb, III, IV NSCLC. (Phase II Portion
      only)

                    
	 
      	 
      
	
                      Customer:

                    	
                      YM
      BIOSCIENCES INC.

                    
	 
      	 
      
	
                      MSA
      #:

                    	
                      YMB07-MSA-17MAY2007

                    
	 
      	 
      
	
                      MSA
      Expiry Date:

                    	
                      Project
      Completion or Termination

                    
	 
      	 
      
	
                      Proposal
      No.:

                    	
                      YMB08-W04-l5DEC2008-3.0

                    
	 
      	 
      
	
                      Customer
      Reference:

                    	
                      YMB08-W04

                    
	 
      	 
      
	
                      Confidentiality:

                    	
                      Restricted
      - Commercial Copyright and Reproduction

                    
	 
      	 
      
	 
      	
                      This
      proposal is submitted by Allphase Clinical Research Inc. in response to
      the invitation issued by Ryan Sukhoo MD, Clinical Project Manager, YM
      BIOSCIENCES INC. It may not be used for any other purposes, reproduced in
      whole or in part, nor passed to any organization or person without the
      specific permission in writing of the President, Allphase Clinical
      Research Services Inc.

                    
	 
      	 
      
	
                      Proposal
      Date:

                    	
                      16DEC2008

                    
	 
      	 
      
	
                      Version:

                    	
                      3.0

                    
	 
      	 
      
	
                      Validity:

                    	
                      90
      days

                    
	 
      	 
      
	
                      CRO
      Address:

                    	
                      Allphase
      Clinical Research Services Inc.

                    
	 
      	
                      1145
      Hunt Club Road, Suite 600

                    
	 
      	
                      Ottawa,
      ON Canada K1V 0Y3

                    
	 
      	
                      P:
      (613) 228-1990 x 100

                    
	 
      	
                      F:
      (6l3) 228-8493

                    
	 
      	
                      C:
      (613) 291-2362

                    
	 
      	
                      Email:
      jsmith@allphaseclinical.com

                    
	 
      	 
      
	

                      Approved
      by:

                    	 
	
                        
      

                    	 
      	 
      	 
      	 
      
	 
      	
                      Jeff
      Smith

                    	 
      	
                      Date

                    	 
      
	 
      	
                      President

                    	 
      	 
      	 
      


            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    
      Page 2 of
36

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

       

    

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    2.
Requested Services

    


    Project
Management

    


    The role
of the Project Manager is critical to the success of every clinical trial. At
Allphase Clinical Research, our project managers are experienced
professionals trained to deliver superior service to our clients. Their
collaborative approach combined with exceptional organizational and
interpersonal skills creates a responsive, client-driven environment. Our
services include:

    
      	
               
      

            	
              ·

            	
              IND/CTA
      maintenance;

            


    

    
      	
               
      

            	
              ·

            	
              Collaborative
      interaction with regulatory authorities and
  IRBs;

            


    

    
      	
               
      

            	
              ·

            	
              Investigator
      site selection and feasibility
assessments;

            


    

    
      	
               
      

            	
              ·

            	
              Regulatory
      document package design (site
level);

            


    

    
      	
               
      

            	
              ·

            	
              Contract
      and budget preparation, negotiation, and
  administration;

            


    

    
      	
               
      

            	
              ·

            	
              Investigator
      meeting organization and site
training;

            


    

    
      	
               
      

            	
              ·

            	
              CRA
      resourcing, mentoring, and co-monitoring
  support;

            


    

    
      	
               
      

            	
              ·

            	
              Monitoring
      report review;

            


    

    
      	
               
      

            	
              ·

            	
              SAE
      reporting coordination;

            


    

    
      	
               
      

            	
              ·

            	
              Coordination
      of site/ vendor/ client communications;
and

            


    

    
      	
               
      

            	
              ·

            	
              Managing
      client expectations for on-time and on-budget
  performance.

            


    

    


    Clinical
Monitoring

    


    Our
Clinical Research Associates (CRAs) are appropriately qualified and industry
recognized for their outstanding reputation in customer service, in-depth
knowledge of industry regulations and guidelines, and therapeutic knowledge.
They ensure compliance with protocols, quality standards, data collection
requirements, and regulatory guidelines. The CRAs are regionally located across
North America, reducing travel time and expenses. Our CRAs truly enjoy their
profession, which we feel is ultimately reflected in their interactions with
clients, colleagues, and site staff as they perform their duties:

    
      	
               
      

            	
              ·

            	
              Site
      initiation, routine monitoring, and
close-out;

            


    

    
      	
               
      

            	
              ·

            	
              Site
      personnel training, mentoring, and
guidance;

            


    

    
      	
               
      

            	
              ·

            	
              Assessing
      protocol compliance and data
integrity;

            


    

    
      	
               
      

            	
              ·

            	
              Regulatory
      document review;

            


    

    
      	
               
      

            	
              ·

            	
              Pharmacy
      training and drug accountability;
and

            


    

    
      	
               
      

            	
              ·

            	
              Ensuring
      GCP, consenting, confidentiality, and safety requirements are
      met.

            


    

    


    Operational
Support

    


    Our
Clinical Operations Associates (COAs) fill a crucial supportive role to all
members of the team. COAs work to streamline the process of managing a clinical
trial. A primary function of this role is acting as a central point through
which virtually all clinical documentation is channeled. As documents are
received, they are logged into a tracking system, scanned, and either filed in
our in-house Trial Master File or forwarded to the client using a transmittal
system. We have developed a proprietary process of managing regulatory
documentation that provides our CRAs with a tool to ensure that site regulatory
files accurately represent the Trial Master File, with a minimal amount of
administration. This means that the site regulatory file is kept up to date, and
our client costs are less than organizations that use more conventional
processes.

    


    COAs also
compile regulatory and enrolment data from investigative sites, which can then
be posted to a secure, client-specific web site. Clients requesting this
value-added service can access a web portal at their convenience, with a
username and password.

    


    CONFIDENTIAL


      
        

      

    

    Page 3 of
36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    The
Manager of Clinical Operations provides high-level quality control by managing
client expectations, employee workloads, oversee compliance with SOPs and
policies, employee performance evaluations, and providing guidance and support
to the team. This supervision creates an environment of consistency and
high-quality work for our clients.

    


    Quality
Assurance

    


    Allphase
Clinical Research Quality Assurance Team strives to provide thorough coverage
for both our internal and external clients' compliance oversight. Our team
brings practical application of the applicable regulations and guidance's to
your attention through carefully planned audits and detailed reports. The
Allphase QA department is at arms-length to the clinical operations team and
reports directly to the President. Independent audits of clinical
investigational sites, in-house processes and documentation provide an objective assessment of the
quality of the data collected and processed as part of a submission. Our
experienced staff provides a comprehensive Quality Assurance service program
including:

    
      	
               
      

            	
              ·

            	
              Evaluation
      and auditing of our quality
processes:

            


    

    
      	
               
      

            	
              o

            	
              Vendor
      qualification and due diligence audits (CROs, central IRBs,
      clinical/diagnostic laboratories, centralized ECG/PFT readers, clinical
      data management, clinical supplies
  distributors);

            


    

    
      	
               
      

            	
              o

            	
              Clinical
      investigator site audits;

            


    

    
      	
               
      

            	
              o

            	
              Clinical
      data management process audits;

            


    

    
      	
               
      

            	
              o

            	
              Clinical
      study report and regulatory submission document
  audits;

            


    

    
      	
               
      

            	
              o

            	
              Systems
      audits (pharmacovigilance and drug safety reporting, computer system
      validation documentation compliance, clinical research
      operations).

            


    

    
      	
               
      

            	
              ·

            	
              Standard
      Operating Procedure (SOP) and policies
  development:

            


    

    
      	
               
      

            	
              o

            	
              Clinical
      research SOP gap analyses and needs
assessment;

            


    

    
      	
               
      

            	
              o

            	
              Facilitation
      of SOP/policies development, approval process, distribution and training
      activities;

            


    

    
      	
               
      

            	
              o

            	
              Collaborative
      design and writing of customized SOPs and
  policies.

            


    

    


    CONFIDENTIAL


      
        

      

    

    Page 4 of
36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    Affiliate
Services

     

    Allphase
Clinical Research is able to offer clients full-service CRO capabilities by
augmenting our in-house services with those of our affiliated partners to
be able to provide:

    
      	
               
      

            	
              ·

            	
              Statistical
      Design and Analysis;

            


    

    
      	
               
      

            	
              ·

            	
              Therapeutically
      aligned Medical Monitoring;

            


    

    
      	
               
      

            	
              ·

            	
              DSMB;

            


    

    
      	
               
      

            	
              ·

            	
              Clinical
      laboratory services;

            


    

    
      	
               
      

            	
              ·

            	
              Investigational
      Product Distribution;

            


    

    
      	
               
      

            	
              ·

            	
              IVRS;

            


    

    
      	
               
      

            	
              ·

            	
              Home
      Health Care network;

            


    

    
      	
               
      

            	
              ·

            	
              Ethics
      Review Boards;

            


    

    
      	
               
      

            	
              ·

            	
              Translation
      services;

            


    

    
      	
               
      

            	
              ·

            	
              Global
      provider network;

            


    

    
      	
               
      

            	
              ·

            	
              DocStorage.ca

            


    

    


    Operational
Support and Web Portal

    


    Our
Clinical Operations Associates (COAs) fill a crucial supportive role to all
members of the team. COAs work to streamline the process of preparing clinical
documents. COAs assist the Medical Writing team to assemble the necessary
components of clinical documents and manage the communication with third party
publishing groups.

    


    As draft
documents are completed, they call be posted to a secure, client-specific web
site. Clients requesting this value-added service can access a secure
bi-directional web portal at their convenience, with a username and password.
Use of this system allows for efficient review of draft documents and alleviates
the need to transfer large attachments across email servers.

    


    Our
Team is Your Team

    


    All of
our in-house services are provided by full-time employees of
Allphase Clinical Research. This permits us to carefully control the quality of
service that we provide, and ensure uniformity in our means and methods. This,
together with the in-house support infrastructure we have created is the reason
for the reliability our clients have come to expect. As a result, our clients
continue to provide us with repeat business every year.

    


    CONFIDENTIAL


      
        

      

    

    Page 5 of
36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    3.
Therapeutic Experience

     

    Allphase
Clinical Research has conducted studies in a variety of therapeutic areas
including:

    


    
      
        
          
            	
                    Therapeutic
      Area

                  	 
      	
                    Indications

                  
	
                    Oncology

                  	 
      	
                    Brain

                    Breast

                    Head
      and Neck

                    Ovarian

                    Renal
      Cell Carcinoma

                    Small
      Cell Lung

                    Colorectal

                    Pediatric
      Glioma

                    Bone
      Marrow Transplant

                    Reduction
      of Neurotoxicity

                  
	
                    Allergy/Respiratory

                  	 
      	
                    Asthma

                    Chronic
      Obstructive Pulmonary Disease

                    Perennial
      Allergic Rhinitis

                    Seasonal
      Allergic Rhinitis

                  
	
                    Cardiovascular

                  	 
      	
                    Atrial
      Fibrillation

                    Deep
      Vein Thrombosis

                    Intermittent
      Claudication

                    Pulmonary
      Embolism

                    Dyslipidemia

                    Atherosclerosis

                    Venous
      Leg Ulcers

                    Hypercholesterolemia

                  
	
                    CNS

                  	 
      	
                    Amytrophic
      Lateral Sclerosis

                    Alzheimer’s
      Disease

                    Depression

                    Multiple
      Sclerosis

                    Smoking
      Cessation

                    Insomnia

                    Stroke

                  
	
                    Endocrinology

                  	 
      	
                    Diabetes

                    Obesity

                  
	
                    Infectious
      Disease

                  	 
      	
                    Hepatitis

                    HIV

                  
	
                    Other

                  	 
      	
                    Alpha-1
      Antitrypsin Deficiency

                    Primary
      Immune Deficiency

                    Post-op
      Pediatric Aggregation Inhibition

                    Thrombotic
      Thrombocytopenic Purpura

                    Dilutional
      Hyponatremia

                    Atopic
      Dermatitis

                  


          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 6 of
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              MSA#:

            	
              YMB07-MSA-17MAY2007

            	
              WO
      Version Code:

            	
              YMB08-WO4-15DEC2008-3.0

            
	
              Version
      Date:

            	
              16DEC2008

            	
              Work
      Order #:

            	
              WO4

            


    

    


    Oncology
Experience

     

    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  	
                                          Therapeutic Area

                                        	 	
                                          Phase

                                        	 	
                                          # of Sites

                                        	 	
                                          # of Subjects

                                        
	
                                          Small
      Cell Lung Cancer

                                        	 	
                                          I/II

                                        	 	
                                          5

                                        	 	
                                          48

                                        
	
                                          Advanced
      Breast Cancer

                                        	 	
                                          II

                                        	 	
                                          5

                                        	 	
                                          30

                                        
	
                                          Metastatic
      Renal Cell Carcinoma

                                        	 	
                                          II

                                        	 	
                                          1

                                        	 	
                                          5

                                        
	
                                          Metastatic
      Breast Cancer

                                        	 	
                                          II

                                        	 	
                                          4

                                        	 	
                                          37

                                        
	
                                          Squamous
      Cell Carcinoma

                                        	 	
                                          II

                                        	 	
                                          6

                                        	 	
                                          20

                                        
	
                                          Squamous
      Cell Carcinoma

                                        	 	
                                          II

                                        	 	
                                          6

                                        	 	
                                          10

                                        
	
                                          Pediatric
      Brain Tumors

                                        	 	
                                          I

                                        	 	
                                          I

                                        	 	
                                          19

                                        
	
                                          Ovarian
      Cancer

                                        	 	
                                          II

                                        	 	
                                          7

                                        	 	
                                          40

                                        
	
                                          Colorectal
      Cancer

                                        	 	
                                          II

                                        	 	
                                          14

                                        	 	
                                          61

                                        
	
                                          Multiple
      Myeloma

                                        	 	
                                          IIb

                                        	 	
                                          10

                                        	 	
                                          50

                                        
	
                                          Multiple
      Myeloma

                                        	 	
                                          III

                                        	 	
                                          10

                                        	 	
                                          50

                                        
	
                                          Pediatric
      Glioma

                                        	 	
                                          II

                                        	 	
                                          6

                                        	 	
                                          44

                                        


                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 7 of
36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    4.
Project Team

     

    YM
BioSciences Inc. has decided to outsource several aspects of their clinical
development plan, and has contacted Allphase Clinical Research Inc. for resource
support and to benefit from our expertise in the conduct of oncology clinical
trials. The selection of an outsourcing partner is a critical step in the
successful execution of any project, as well as integral to the external
perception of the sponsor company.

    


    Allphase
has a proven track record of successfully conducting research trials for our
clients, as demonstrated by the 100% repeat
business our clients provide. In addition to
task competence, Allphase also focuses on relationships, both with our
clients and with the investigative site staff. Establishing a positive
environment with future product prescribers is an important adjunct to the
marketing initiatives of our clients.

    


    In order
to meet the objectives of your project, a qualified Project Manager will be responsible
for the overall execution of the trial. This person will be supported by an
experienced and multi-talented team of CRA's, Regulatory Affairs personnel,
Medical Writers, Drug Safety, Data Management and operational staff. The
proposed team members are noted below however, the availability of proposed
staff is dependent on project initiation timelines.

    


    Project
Management

    


    Wendy
Kerby, RN: Sr. Project Manager (Ottawa)

    


    Ms. Kerby
has over 20 years of research experience primarily in the CRO industry and as a
research nurse/study coordinator at a major Canadian University. Ms. Kerby
offers experience in Clinical Study Monitoring, Project Management, Audit
Preparation, SOP development, CRF development and vendor relations. She has an
excellent knowledge of Good Clinical Practices (GCP), FDA, Health Canada and ICH
guidelines and regulations. Ms. Kerby is a highly motivated individual with a
strong capability for multi-tasking and prioritizing. She has an excellent
working knowledge of the following therapeutic areas: oncology/haematology,
immunology, rheumatology, neurology and infectious diseases. She has also
presented at various Investigator meetings, conducted study specific training
and presented at internal/company meetings.

    


    Ms. Kerby
has over 15 years experience as a bedside nurse and clinic nurse, having worked
in the oncology clinic setting, haematology, paediatrics and emergency. She has
worked as a research nurse/study coordinator in oncology for 10 years, with
emphasis on Lung cancer, Colorectal Cancer, Melanoma, Breast and the various
Haematological disorders, both for industry conducted studies and co-operative
group studies.

    


    The CRO
experience has seen Ms. Kerby in the following roles: CRA, Lead CRA and Project
Manager. She brings over 7 years experience into the project management role and
has managed 4 international oncology studies in colorectal (2), melanoma and
ovarian cancer.

    


    CONFIDENTIAL


      
        

      

    

    Page 8 of
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                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    Clinical
Research Associates

    


    Karry
Schenk (Ottawa, ON)

    


    Ms.
Schenk has been a CRA for over 10 years and has monitored 7 oncology studies.
Prior to this she worked for 4 years as a study coordinator at a cancer clinic.
Ms. Schenk worked on more than 100 oncology studies during this time, 15 of
which were colorectal studies. She also worked on a part time basis for 1 year
with the NCIC doing randomizations.

    


    Faye
Aspelund (Ottawa, ON)

    


    Ms.
Aspelund has been a CRA for 2.5 years. Prior to this she worked for 15 years as
an oncology study coordinator. Ms. Aspelund worked on more than 200 oncology
studies during this time, 30 of which were colorectal studies.

    


    Heather
Kimber, RN (Toronto, ON)

    


    Ms.
Kimber has a strong background in oncology, including 7 years of direct oncology
patient care in both an inpatient and ambulatory setting. She was an instructor
for the Oncology Certificate Program at Sheridan College and has 10 years of
clinical research coordinator experience. Ms. Kimber successfully completed the
Allphase Center of Excellence (ACE) CRA Training program in June, 2007 and has
been monitoring oncology studies since that time.

    


    Fredy
Perez, MD (Vancouver, BC)

    


    Dr. Perez
obtained his Medical Doctorate in Peru in 2002, followed by a Masters in Disease
Control. Dr. Perez has been a CRA for 4 years and has worked in multiple
therapeutic areas including colorectal and breast cancer. Dr. Perez is a member
of the Society of Clinical Research Associates (SoCRA) and the Clinical Research
Professionals of British Columbia (CRPBC). Dr. Perez' previous work experience
also includes being a clinical research coordinator and some work in Drug Safety
and Pharmacovigilance.

    


    Clinical
Operations Associates

    


    Alison
Conley (Ottawa, ON)

    


    Ms.
Conley is our most senior Clinical Operations Associate with more than five
years of clinical research experience, primarily responsible for organizing
Investigator Meetings. Ms. Conley is an administrative professional who
possesses strong organizational skills and is praised by existing clients for
her proactive, friendly approach. A dedicated project specific COA will also be
assigned to manage the administrative aspect of the project including regulatory
document collection, minutes, document processing and Trial Master File
management.

    


    Litharitza
Vakopoulos (Ottawa, ON)

    


    Ms.
Vakopoulos has been providing Clinical Operations support for over 5 years. She
has thorough knowledge of ICH and local regulatory authority regulations
regarding clinical research and development. Ms. Vakopoulos has been responsible
for supporting study start-up activities, clinical status tracking, and
in-house site management on numerous oncology studies.

    


    CONFIDENTIAL


      
        

      

    

    Page 9 of
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                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    Compliance
and Quality Assurance

     

    Linda
Kraft, RN, Manager, Compliance and Quality Assurance (Ottawa, ON)

    


    Ms. Kraft
is based in Ottawa and brings with her more than 13years experience in clinical
research including project management and auditing. Mrs. Kraft has several years
of experience in conducting central file assessments, and site and sponsor
audits.

    


    Diane
Motink, MLT; Sr. Compliance and Quality Assurance Specialist (Mississauga,
ON)

    


    Ms.
Motink has 9 years experience in pharmaceutical related quality control roles, 5
of which are as a quality assurance professional.

    


    Consultants

    


    Medical
Monitoring and Biostatistics are the only Allphase managed outsourced functions
anticipated for this project. Client will be consulted regarding the choice of
sub-contractor if and as needed.

    


    Contacts

    


    
      
        
          
            
              	
                      Technical
      Contact

                    	
                      Administrative
      Contact

                    
	
                      Wendy
      Kirby, RN.,

                    	
                      Anne
      Gamache

                    
	
                      Sr.
      Project Manager

                    	
                      Project
      Analyst

                    
	
                      Allphase
      Clinical Research Inc.

                    	
                      Allphase
      Clinical Research Inc.

                    
	
                      1145
      Hunt Club K1V 0Y3

                    	
                      1145
      Hunt Club K1V 0Y3

                    
	
                      Tel:
      613-228-1990 x 117

                    	
                      Tel:
      613-228-1990 x 136

                    
	
                      Fax:
      613-228-8493

                    	
                      Fax:
      613-228-8493

                    
	
                      Cell:
      613-808-4768

                    	
                      Email:
      agamache@allphaseclinical.com

                    
	
                      Email:
      wkerby@allphaseclinical.com

                    	 
      


            

          

        

      

    

     

    CONFIDENTIAL


      
        

      

    

    Page 10
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    4.
SOPs

     

    YM
BioSciences Inc. has decided to use the following Allphase SOPs for this
project:

    


    
      
        
          
            
              
                
                  	
                          Related Area

                        	 
      	
                          Title of SOP

                        	 
      	
                          Effective Date

                        
	
                          Quality
      Assurance (QA)

                        	 
      	 
      	 
      	 
      
	
                          QA
      006.01

                        	 
      	
                          Investigator
      Site Audits

                        	 
      	
                          03-DEC-2007

                        
	
                          QA
      008.00

                        	 
      	
                          Fraud
      or Scientific Misconduct

                        	 
      	
                          15-JUN-2007

                        
	
                          Clinical
      Research (CR or CO)

                        	 
      	 
      	 
      	 
      
	
                          CR
      100.00

                        	 
      	
                          Preparing,
      Maintaining and archiving of the Trial Master File

                        	 
      	
                          27-MAR-2006

                        
	
                          CR
      104.00

                        	 
      	
                          Investigator
      Site Selection

                        	 
      	
                          27-MAR-2006

                        
	
                          CO
      105.01

                        	 
      	
                          Translation
      of Clinical Study Documents

                        	 
      	
                          07-NOV-2008

                        
	
                          CO
      106.01

                        	 
      	
                          Investigator
      Meetings

                        	 
      	
                          18-SEP-2008

                        
	
                          CR
      107.00

                        	 
      	
                          Investigator
      Financial Agreements

                        	 
      	
                          15-JUN-2006

                        
	
                          CR
      108.00

                        	 
      	
                          Site
      Initiation Visit

                        	 
      	
                          01-JUN-2006

                        
	
                          CO
      109.03

                        	 
      	
                          Interim
      Monitoring Visit

                        	 
      	
                          31-OCT-2007

                        
	
                          CR
      110.00

                        	 
      	
                          Close-Out
      Visit

                        	 
      	
                          10-JUN-2006

                        
	
                          CO
      111.01

                        	 
      	
                          Source
      Document versus Case Report Form

                        	 
      	
                          06-MAY-2008

                        
	
                          CO
      112.00

                        	 
      	
                          Source
      Data Verification and Case Report Form Review

                        	 
      	
                          18-JUL-2008

                        
	
                          CO
      113.01

                        	 
      	
                          Protocol
      Deviations

                        	 
      	
                          11-JUL-2008

                        
	
                          CO
      114.01

                        	 
      	
                          Recording
      and Reporting Adverse Events

                        	 
      	
                          06-AUG-2008

                        
	
                          CO
      115.01

                        	 
      	
                          The
      Archiving and Shipping of the Trial Master File

                        	 
      	
                          09-SEP-2008

                        
	
                          CO
      118.00

                        	 
      	
                          Premature
      Termination or Suspension of a Clinical Trial

                        	 
      	
                          29-JUL-2008

                        
	
                          CO
      119.00

                        	 
      	
                          Data
      Clarification

                        	 
      	
                          03-APR-2008

                        
	
                          CO
      120.00

                        	 
      	
                          Investigational
      Product Accountability

                        	 
      	
                          09-OCT-2008

                        
	
                          CO
      121.00

                        	 
      	
                          Site
      Transfer between Clinical Research Associates

                        	 
      	
                          12-NOV-2008

                        
	
                          CO
      122.00

                        	 
      	
                          Monitoring
      Plan

                        	 
      	
                          24-JUN-2008

                        
	
                          CO
      123.00

                        	 
      	
                          Distribution
      and Tracking of Investigator’s Brochure

                        	 
      	
                          24-JUN-2008

                        
	
                          CO
      124.00

                        	 
      	
                          TMF
      Document Retrieval

                        	 
      	
                          09-SEP-2008

                        
	
                          CO
      126.00

                        	 
      	
                          Data
      safety Monitoring Boards

                        	 
      	
                          19-JAN-2009

                        
	
                          Scientific
      Affairs (SA)

                        	 
      	 
      	 
      	 
      
	
                          SA
      600.01

                        	 
      	
                          Clinical
      Study Report

                        	 
      	
                          19-NOV-2008

                        
	
                          SA
      601.01

                        	 
      	
                          Statistical
      Analysis Plan

                        	 
      	
                          19-NOV-2008

                        
	
                          Drug
      Safety (DS)

                        	
                            

                        	
                          Recording
      and Reporting of Serious Adverse Events and Reporting of Safety
      Information Externally

                        	
                            

                        	
                          10-NOV-2006

                        


                

              

            

          

        

      

    

    


    To be
determined in discussion with Client

    


    CONFIDENTIAL


      
        

      

    

    Page 11
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    5.
Project Summary

     

    The
following summary outlines the key elements of the study which have been
provided to date. This proposal is based on the accuracy of these items. Should
any facts and/or assumptions be incorrect, Allphase reserves the right to modify
this proposal to reflect any new information.

    


    
      
        	
                Protocol

              	 
      	 
      	 
      	 
      
	
                Sponsor

              	 
      	 
      	 
      	
                YM
      BIOSCIENCES INC.

              
	
                Protocol
      Number

              	 
      	 
      	 
      	
                YMB
      1000-010

              
	
                Protocol
      Version

              	 
      	 
      	 
      	
                November
      18th,
      2008 - version 1.0

              
	
                Drug

              	 
      	 
      	 
      	
                Nimotuzumab
      (TheraCIM h-R3) from CIMYM

              
	
                Indication

              	 
      	 
      	 
      	
                Stage
      IIb,III,IV non-small cell lung cancer

              
	
                Phase

              	 
      	 
      	 
      	
                III

              
	
                Title

              	 
      	 
      	 
      	
                A
      Phase I-II clinical study of Nimotuzumab (TheraCIM-h-R3) in combination
      with external radiotherapy in stage IIb, III, IV NSCLC. (Phase II Portion
      only)

              
	
                Short
      Title

              	 
      	 
      	 
      	
                TBD

              
	
                Objectives
      for Phase I component

              	 
      	 
      	 
      	
                Primary: To evaluate the
      safety and feasibility of the administration of nimotuzumab with
      palliative radiation in patients who are unsuitable for radical therapy
      (curative intent chemo radiation)

              
	
                Objectives
      for Phase II component

              	 
      	 
      	 
      	
                Primary: 1) To assess
      the overall survival (median survival time) in patients treated with
      nimotuzamab in combination with palliative radiation vs radiation alone.
      2) To assess the local and systemic response rates produced by nimotuzamab
      in combination with palliative radiation vs radiation alone in patients
      with NSCLC stage IIb, III, and IV. Stage II/able for radical therapy
      (either radiation or chemo radiation). 3) To evaluate quality of life in
      patients receiving nimotuzamab in combination with radiation compared to
      radiation alone.

              
	
                Sites
      & Start Up Meetings

              	 
      	 
      	 
      	 
      
	
                No.
      of Local Investigator Meetings

              	 
      	
                1

              	 
      	
                Ottawa

              
	
                Local
      Investigator Meeting Attendance (hrs)

              	 
      	
                16

              	 
      	
                2
      days; 1 day workshop with coordinators

              
	
                PM

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                CRA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Quality
      Assurance (ACE)

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                COA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Medical
      Monitor

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Local
      Kick off Meeting

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                PM

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                CRA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                COA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Medical
      Monitor

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Protocol
      Review Process

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                PM

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Director
      of Scientific Affairs

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              


      

    

     

    
      CONFIDENTIAL


        
          

        

      

      Page 12
of 36

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        	
                CRA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                COA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Medical
      Monitor

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Mid
      Study Local Team Meeting

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                PM

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                CRA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                COA

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                Medical
      Monitor

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                #
      of Treatment Groups

              	 
      	
                1

              	 
      	
                2
      arms in phase II

              
	
                Local
      or Central IRB

              	 
      	
                Local

              	 
      	 
      
	
                #
      of Sites to be Managed by Allphase

              	 
      	
                20

              	 
      	
                All
      Canadian

              
	
                #
      of Sites to be Monitored by Allphase

              	 
      	
                20

              	 
      	 
      
	
                Percentage
      of Subjects to be Monitored

              	 
      	
                100

              	 
      	 
      
	
                Feasibility
      Survey

              	 
      	
                Y

              	 
      	
                Y/N

              
	
                #
      of Sites for Feasibility Survey

              	 
      	
                20

              	 
      	
                YMB
      responsibility - Allphase to Assist

              
	
                #
      of Sites Selection Visits (CRA)

              	 
      	
                0

              	 
      	
                TBD

              
	
                #
      of Sites Selection Visits (PM)

              	 
      	
                0

              	 
      	 
      
	
                #
      of Sites Initiation Visits (CRA)

              	 
      	
                20

              	 
      	 
      
	
                #
      of Sites Initiation Visits (PM)

              	 
      	
                4

              	 
      	
                One
      per CRA

              
	
                Est.
      # of Monitoring Hrs/non-evaluable pt.

              	 
      	
                6

              	 
      	 
      
	
                Est.
      # of Monitoring Hrs/screen failure pt.

              	 
      	
                1

              	 
      	
                Assuming
      minimal data collection

              
	
                Est.
      # of Monitoring Hrs/Completed CRF

              	 
      	
                20

              	 
      	 
      
	
                Est.
      # of Hrs/Visit Report

              	 
      	
                5

              	 
      	 
      
	
                Estimated
      # of Monitoring Hours

              	 
      	
                2573

              	 
      	 
      
	
                Estimated
      # of Monitoring Days

              	 
      	
                368

              	 
      	 
      
	
                Estimated
      # of Monitoring Visits

              	 
      	
                258

              	 
      	
                Assume
      30% of visits can be multi-day visits considering both projects (1000-10
      & 1000-08-0202) having many of the same sites

              
	
                Estimated
      % of 1 day Monitoring Visits

              	 
      	
                70%

              	 
      	 
      
	
                Estimated
      Monitoring Frequency

              	 
      	
                6

              	 
      	
                Weeks

              
	
                Estimated
      # of CRAs

              	 
      	
                4

              	 
      	
                Regionally
      based in Canada

              
	
                Estimated
      # of Close-out Visits

              	 
      	
                20

              	 
      	 
      
	
                Subjects

              	 
      	 
      	 
      	 
      
	
                Number
      of Subjects Randomized locally

              	 
      	
                128

              	 
      	 
      
	
                Screen
      Failure Rate

              	 
      	
                10%

              	 
      	 
      
	
                Drop
      Out Rate (once Randomized)

              	 
      	
                0%

              	 
      	 
      
	
                #
      of Subjects Evaluable locally

              	 
      	
                128

              	 
      	 
      
	
                #
      of Subjects Screened locally

              	 
      	
                141

              	 
      	 
      
	
                Enrolment
      Period

              	 
      	
                82

              	 
      	 
      


      

    

     

    
      CONFIDENTIAL


        
          

        

      

      Page 13
of 36

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        	
                Duration
      of Each Subject

              	 
      	
                52

              	 
      	 
      
	
                Total
      Study Duration (all subjects)

              	 
      	
                134

              	 
      	 
      
	
                Project
      Administration

              	 
      	 
      	 
      	 
      
	
                #
      PMs for project

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                #
      COAs for project

              	 
      	
                1

              	 
      	 
      
	
                #
      of collaborating CROs

              	 
      	
                0

              	 
      	 
      
	
                Total
      Study Duration (PM)

              	 
      	
                148

              	 
      	
                weeks

              
	
                Estimated
      # PM hours/week/site

              	 
      	
                0.5

              	 
      	 
      
	
                Estimated
      # PM hours/week

              	 
      	
                10

              	 
      	 
      
	
                Estimated
      # CRA Admin Hrs/week/site

              	 
      	
                0.5

              	 
      	 
      
	
                Estimated
      # CRA Admin Hrs/week

              	 
      	
                10

              	 
      	 
      
	
                Estimated
      # COA Admin Hrs/week/site

              	 
      	
                0.75

              	 
      	 
      
	
                Estimated
      # COA Admin Hrs/week

              	 
      	
                15

              	 
      	 
      
	
                Estimated
      # Doc Man. Admin Hrs/Site/Week

              	 
      	
                0.5

              	 
      	 
      
	
                Estimated
      # Doc Man. Admin Hrs/Week

              	 
      	
                10

              	 
      	 
      
	
                Team
      Teleconferences

              	 
      	
                2

              	 
      	
                1=Weekly;
      2=bi-weekly, 4=monthly

              
	
                #
      of Teleconferences

              	 
      	
                74

              	 
      	 
      
	
                Estimated
      # Hrs/Teleconference/CRA

              	 
      	
                0.75

              	 
      	 
      
	
                PM
      Teleconferences (with Sponsor)

              	 
      	
                1

              	 
      	
                1=Weekly;
      2=bi-weekly, 4=monthly

              
	
                Number
      of PM Teleconferences (Sponsor)

              	 
      	
                148

              	 
      	 
      
	
                Estimated
      # Hrs/Teleconference (Sponsor)

              	 
      	
                1

              	 
      	 
      
	
                PM
      Ad hoc visits/quarter

              	 
      	
                1

              	 
      	 
      
	
                Estimated
      # of PM Ad-Hoc Visits

              	 
      	
                12

              	 
      	 
      
	
                Estimated
      # of Co-Visits by PM

              	 
      	
                4

              	 
      	 
      
	
                Medical
      Writing

              	 
      	 
      	 
      	 
      
	
                Medical
      Writing Research and Therapeutic Training

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                Regulatory
      Affairs

              	 
      	 
      	 
      	 
      
	
                Pre
      CTA Meeting with Health Canada

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                Submission
      to Health Canada

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                Estimated
      # of HC Amendments

              	 
      	
                0

              	 
      	 
      
	
                Safety

              	 
      	 
      	 
      	 
      
	
                Medical
      Oversight by Allphase?

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                #
      of subjects for Safety

              	 
      	
                128

              	 
      	 
      
	
                Estimated
      Percentage of SAEs

              	 
      	
                50%

              	 
      	 
      
	
                Estimated
      # of SAEs

              	 
      	
                64

              	 
      	 
      
	
                Estimated
      Percentage of Reportable SAEs

              	 
      	
                20%

              	 
      	
                Percentage
      of SAEs requiring regulatory
reporting

              


      

    

     

    
      CONFIDENTIAL


        
          

        

      

      Page 14
of 36

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        	
                Estimated
      # of Reportable SAEs

              	 
      	
                13

              	 
      	 
      
	
                Teleconferences

              	 
      	
                13

              	 
      	
                1=Weekly;
      2=bi-weekly, 4=monthly, 8=bi-monthly, 13=quarterly

              
	
                #
      of Teleconferences with Sponsor

              	 
      	
                11

              	 
      	 
      
	
                Management
      of DSMB

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1

              
	
                #
      of DSMB meetings

              	 
      	
                3

              	 
      	 
      
	
                Estimated
      AEs/Randomized Subject

              	 
      	
                10

              	 
      	 
      
	
                Estimated
      Medical terms for Manual Coding/Subject

              	 
      	
                10

              	 
      	 
      
	
                Data
      Management

              	 
      	 
      	 
      	 
      
	
                Data
      Management Involvement?

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                BioStatistics

              	 
      	 
      	 
      	 
      
	
                Biostatistics
      Involvement?

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                Quality
      Assurance

              	 
      	 
      	 
      	 
      
	
                Site
      Audits

              	 
      	
                3

              	 
      	 
      
	
                TMF
      Audit

              	 
      	
                0

              	 
      	 
      
	
                Vendor
      Management

              	 
      	 
      	 
      	 
      
	
                Central
      Lab Managed by Allphase?

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = Number of labs

              
	
                Imaging
      Lab Managed by Allphase?

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = Number if labs

              
	
                Investigational
      Product Distributor Managed by Allphase?

              	 
      	
                0

              	 
      	
                No
      = 0; Yes = 1

              
	
                SOP

              	 
      	 
      	 
      	 
      
	
                Allphase
      SOPs to be used?

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1 (expand group)

              
	
                Allphase
      Forms?

              	 
      	
                1

              	 
      	
                No
      = 0; Yes = 1 (expand group)

              
	
                Services
      Requested

              	 
      	 
      	 
      	 
      
	 
      	 
      	 
      	 
      	
                Regulatory

              
	 
      	 
      	
                YMB

              	 
      	
                CTA
      prep, submission and maintenance

              
	 
      	 
      	 
      	 
      	
                Project
      Management

              
	 
      	 
      	
                YMB

              	 
      	
                Site
      Contract Negotiation

              
	 
      	 
      	
                ACR

              	 
      	
                Site
      Payment Facilitation

              
	 
      	 
      	
                ACR

              	 
      	
                Regulatory
      Document Collection

              
	 
      	 
      	
                ACR

              	 
      	
                Trial
      Master File Set-up & Maintenance

              
	 
      	 
      	
                ACR

              	 
      	
                ICF
      Preparation & Translation

              
	 
      	 
      	
                ACR

              	 
      	
                IRB
      preparations and submissions - central IRB; or assistance with the
      submissions if local IRB.

              
	 
      	 
      	
                YMB

              	 
      	
                Site
      Identification

              
	 
      	 
      	
                ACR

              	 
      	
                Multi-site
      Management

              
	 
      	 
      	
                ACR

              	 
      	
                CRA
      Management

              
	 
      	 
      	
                ACR

              	 
      	
                Teleconference
      and Project Updates

              
	 
      	 
      	
                YMB

              	 
      	
                Vendor
      Management (if applicable)

              
	 
      	 
      	
                ACR

              	 
      	
                General
      Administration

              
	 
      	 
      	 
      	 
      	
                Investigator
      Meeting - North America

              
	 
      	 
      	
                ACR

              	 
      	
                Attendance

              


      

    

     

    
      CONFIDENTIAL


        
          

        

      

      Page 15
of 36

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        	 
      	 
      	
                ACR

              	 
      	
                Planning
      & Execution

              
	 
      	 
      	
                ACR

              	 
      	
                Presentations

              
	 
      	 
      	
                ACR

              	 
      	
                Travel
      Arrangements for Attendees

              
	 
      	 
      	 
      	 
      	
                Clinical
      Monitoring

              
	 
      	 
      	
                ACR

              	 
      	
                Pre-Study
      Visits (new sites only)

              
	 
      	 
      	
                ACR

              	 
      	
                Site
      Initiation

              
	 
      	 
      	
                ACR

              	 
      	
                Interim
      Monitoring & Site management

              
	 
      	 
      	
                ACR

              	 
      	
                Site
      Close Out

              
	 
      	 
      	 
      	 
      	
                Safety

              
	 
      	 
      	
                ACR

              	 
      	
                Safety
      Plan

              
	 
      	 
      	
                ACR

              	 
      	
                CIOMS/MedWatch
      report prep

              
	 
      	 
      	
                ACR

              	 
      	
                SAE
      alert reporting to authorities

              
	 
      	 
      	 
      	 
      	
                Data
      Management/Biostatistics

              
	 
      	 
      	
                YMB

              	 
      	
                CRF
      Design & Build

              
	 
      	 
      	
                YMB

              	 
      	
                DM
      System Set Up (include edit checks)

              
	 
      	 
      	
                YMB

              	 
      	
                Data
      Validation and Review CRFs

              
	 
      	 
      	
                YMB

              	 
      	
                Data
      Query

              
	 
      	 
      	
                YMB

              	 
      	
                Coding
      AE & Medications

              
	 
      	 
      	
                YMB

              	 
      	
                Interim
      Analysis Plan

              
	 
      	 
      	
                YMB

              	 
      	
                Final
      Analysis Plan

              
	 
      	 
      	
                YMB

              	 
      	
                Randomization
      Services

              
	 
      	 
      	
                ACR

              	 
      	
                Medical
      Monitoring

              
	 
      	 
      	 
      	 
      	
                Data
      Monitoring Committee

              
	 
      	 
      	
                ACR

              	 
      	
                Establish
      Committee and Organize Meetings

              
	 
      	 
      	 
      	 
      	
                Medical
      Writing

              
	 
      	 
      	
                YMB

              	 
      	
                Protocol
      Development

              
	 
      	 
      	
                YMB

              	 
      	
                Interim
      & Final Clinical Study Reports

              
	 
      	 
      	
                YMB

              	 
      	
                Manuscripts

              
	 
      	 
      	 
      	 
      	
                Quality
      Assurance

              
	 
      	 
      	
                ACR

              	 
      	
                GCP
      Investigator/Site/Vendor Audit

              
	 
      	 
      	
                TBD

              	 
      	
                QA
      Audit of Clinical Database

              
	 
      	
                  

              	
                TBD

              	
                  

              	
                QA
      Audit of Clinical Study
Report

              


      

    

    


    Project
Timelines

    


    
      
        
          
            	
                    Activity

                  	 
      	
                    Date of Completion

                  
	
                    Executed
      LOI

                  	 
      	
                    Dec-08

                  
	
                    Fully
      Executed Contract

                  	 
      	
                    Dec-08

                  
	
                    Kick-off
      Meeting

                  	 
      	
                    Jan-08

                  
	
                    Site
      Selection

                  	 
      	
                    Jan-08

                  
	
                    IRB
      Submissions

                  	 
      	
                    Jan-09

                  
	
                    Investigator
      Agreements

                  	 
      	
                    Jan-09

                  
	
                    Investigator
      Meeting

                  	 
      	
                    Feb-09

                  
	
                    First
      SIV

                  	 
      	
                    Mar-09

                  
	
                    First
      Subject First Visit

                  	 
      	
                    Mar-09

                  
	
                    Last
      Subject First Visit

                  	 
      	
                    Sep-10

                  


          

        

      

    

    
      
        	
                Last
      Subject Last Visit

              	 
      	
                Sep-11

              
	
                Data
      Base Lock

              	 
      	
                Nov-11

              
	
                Final
      Close-Out Visit

              	 
      	
                Nov-11

              
	
                Final
      Clinical Study Report

              	
                  

              	
                Dec-11

              


      

    

     

    
      CONFIDENTIAL


        
          

        

      

      Page 16
of 36


      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

       

      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

       

    

    
      
        	
                Start-Up
      Duration

              	 	
                9

              
	
                Enrolment

              	 	
                82

              
	
                Treatment
      period

              	 	
                52

              
	
                Close
      Out (DBL to CSR)

              	 	
                5

              
	
                Total
      Subject Duration

              	 	
                134

              
	
                Total
      Study Duration (PM)

              	 	
                148

              
	
                Data
      Management Duration

              	 	
                138

              


      

    

    


    Roles
and Rates

    


    
      
        
          
            
              
                
                  	
                          Allphase Role

                        	 	
                          Allphase Resource

                        	 	
                          Hourly Rate (CDN)

                        	 
	
                          DE

                        	 	
                          Data
      Entry Personnel

                        	 	$	65	 
	
                          DOC

                        	 	
                          Document
      Management

                        	 	$	75	 
	
                          COA

                        	 	
                          Clinical
      Operations Associate

                        	 	$	75	 
	
                          CRA

                        	 	
                          Clinical
      Research Associate

                        	 	$	90	 
	
                          LCRA

                        	 	
                          Lead
      Clinical Research Associate

                        	 	$	95	 
	
                          DM

                        	 	
                          Data
      Manager

                        	 	$	100	 
	
                          MW

                        	 	
                          Medical
      Writing

                        	 	$	100	 
	
                          PM

                        	 	
                          Project
      Manager

                        	 	$	100	 
	
                          RA

                        	 	
                          Regulatory
      Affairs

                        	 	$	100	 
	
                          DS

                        	 	
                          Drug
      Safety

                        	 	$	100	 
	
                          QA

                        	 	
                          Quality
      Assurance Auditor

                        	 	$	100	 
	
                          DIR

                        	 	
                          Director
      Scientific Affairs

                        	 	$	120	 
	
                          BIO

                        	 	
                          Biostatistician

                        	 	$	130	 
	
                          ACE

                        	 	
                          Trainer

                        	 	$	150	 
	
                          MMD

                        	 	
                          Medical
      Monitor Data Management

                        	 	$	200	 
	
                          MM

                        	 	
                          Medical
      Monitor

                        	 	$	350	 


                

              

            

          

        

      

    

    


    Project
Details

    


    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  
                                    	
                                            List of Tasks

                                          	 
      	
                                            YMB

                                          	 
      	
                                            Allphase

                                          	 
      	
                                            ADM

                                          	 
      	
                                            Task

                                            Hours

                                          	 
      	
                                            Units

                                          	 
      	
                                            Total

                                            Hours

                                          	 
      	
                                            Resp

                                          	 
	
                                            Pre-Study
      Activities

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Project
      Feasibility Study

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Identify
      sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Contact
      sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Draft
      CDA for sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Develop
      Feasibility Survey

                                          	 
      	
                                            (X)

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	
                                            4

                                          	 
      	
                                            1

                                          	 
      	
                                            4

                                          	 
      	
                                            PM

                                          	 
	
                                            Distribute
      CDA to sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Distribute
      Feasibility to sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                            Collect
      and review CDA/Feasibilities from sites

                                          	 
      	
                                            X

                                          	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 


                                  

                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 17
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        
          
            
              
                	
                        Review
      Feasibilities from sites

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        0.5

                      	 
      	
                        20

                      	 
      	
                        10

                      	 
      	
                        PM

                      	 
	
                        Compile
      Feasibility Report

                      	 
      	
                        X

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        PM

                      	 
	
                        Protocol
      Development

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Protocol
      Ammendments (if required)

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Compilation
      & update IB

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Kick-off
      meeting

                      	 
      	
                        X

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        PM
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        PM

                      	 
	
                        PM
      travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        PM

                      	 
	
                        CRA
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        CRA
      travel time (average)

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        COA
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        COA

                      	 
	
                        COA
      travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        COA

                      	 
	
                        Medical
      Monitor attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        MM

                      	 
	
                        Medical
      Monitor travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        3

                      	 
      	
                        1

                      	 
      	
                        3

                      	 
      	
                        MM

                      	 
	
                        International
      Kick-Off Meeting

                      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Mid
      Study Local Team Meeting

                      	 
      	
                        X

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        PM
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        PM

                      	 
	
                        PM
      travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        PM

                      	 
	
                        CRA
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        CRA
      travel time (average)

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        COA
      attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        COA

                      	 
	
                        COA
      travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        COA

                      	 
	
                        Medical
      Monitor attendance

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        MM

                      	 
	
                        Medical
      Monitor travel time

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        3

                      	 
      	
                        1

                      	 
      	
                        3

                      	 
      	
                        MM

                      	 
	
                        Protocol
      Review Process

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        PM

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        PM

                      	 
	
                        Director
      Scientific Affairs

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        DIR

                      	 
	
                        CRA

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        4

                      	 
      	
                        16

                      	 
      	
                        CRA

                      	 
	
                        COA

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        COA

                      	 
	
                        Medical
      Monitor

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        MM

                      	 
	
                        Regulatory
      Management – study

                      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Vendor
      Management

                      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Local
      Investigator Meeting

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Identify
      location and conduct preliminary investigation of costs;
      reservations

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        COA

                      	 
	
                        Organize
      travel & hotel for study team

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        12

                      	 
      	
                        1

                      	 
      	
                        12

                      	 
      	
                        COA

                      	 
	
                        Plan
      and organize IM

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        40

                      	 
      	
                        1

                      	 
      	
                        40

                      	 
      	
                        PM

                      	 
	
                        Teleconferences
      – PM

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        5

                      	 
      	
                        5

                      	 
      	
                        PM

                      	 
	
                        Teleconferences
      – COA

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        5

                      	 
      	
                        5

                      	 
      	
                        COA

                      	 
	
                        Prepare
      agenda

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        PM

                      	 


              

            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 18
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        
          
            
              
                	
                        Prepare
      presentations

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        16

                      	 
      	
                        1

                      	 
      	
                        16

                      	 
      	
                        PM

                      	 
	
                        Design
      Investigator Meeting materials

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        12

                      	 
      	
                        1

                      	 
      	
                        12

                      	 
      	
                        PM

                      	 
	
                        Prepare
      Investigator Meeting materials

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        24

                      	 
      	
                        1

                      	 
      	
                        24

                      	 
      	
                        COA

                      	 
	
                        Prepare
      welcome letters, name tags, materials

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        16

                      	 
      	
                        1

                      	 
      	
                        16

                      	 
      	
                        COA

                      	 
	
                        Attendance
      &  presentations at Meeting

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        PM
      prep

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        1

                      	 
      	
                        2

                      	 
      	
                        PM

                      	 
	
                        PM
      travel

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        1

                      	 
      	
                        2

                      	 
      	
                        PM

                      	 
	
                        PM
      Presentation & Attendance

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        16

                      	 
      	
                        1

                      	 
      	
                        16

                      	 
      	
                        PM

                      	 
	
                        CRA
      prep

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        4

                      	 
      	
                        8

                      	 
      	
                        CRA

                      	 
	
                        CRA
      travel

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        CRA
      attendance

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        16

                      	 
      	
                        4

                      	 
      	
                        64

                      	 
      	
                        CRA

                      	 
	
                        ACE
      Trainer prep

                      	 
      	 
      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        QA

                      	 
	
                        ACE
      Trainer travel

                      	 
      	 
      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        QA

                      	 
	
                        ACE
      Trainer presentation & attendance

                      	 
      	 
      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        QA

                      	 
	
                        COA
      prep & oversight

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        24

                      	 
      	
                        1

                      	 
      	
                        24

                      	 
      	
                        COA

                      	 
	
                        COA
      travel

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        1

                      	 
      	
                        2

                      	 
      	
                        COA

                      	 
	
                        COA
      attendance

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        16

                      	 
      	
                        1

                      	 
      	
                        16

                      	 
      	
                        COA

                      	 
	
                        Medical
      Monitor prep

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        1

                      	 
      	
                        2

                      	 
      	
                        MM

                      	 
	
                        Medical
      Monitor travel

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        1

                      	 
      	
                        2

                      	 
      	
                        MM

                      	 
	
                        Medical
      Monitor Presentation & Attendance

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        MM

                      	 
	
                        Ethics

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Preparation
      of ICF template

                      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Customization
      of ICF (PIPEDA)

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        20

                      	 
      	
                        20

                      	 
      	 
      	 
	
                        Preparation
      of other subject materials

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        12

                      	 
      	
                        1

                      	 
      	
                        12

                      	 
      	
                        PM

                      	 
	
                        Assist
      sites with submissions

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        20

                      	 
      	
                        20

                      	 
      	
                        PM

                      	 
	
                        IRB
      approval review & action if needed

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        20

                      	 
      	
                        20

                      	 
      	
                        PM

                      	 
	
                        Translation
      of ICF & materials

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        6

                      	 
      	
                        1

                      	 
      	
                        6

                      	 
      	
                        PM

                      	 
	
                        Subsequent
      ICF revisions (amendments)

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        6

                      	 
      	
                        1

                      	 
      	
                        6

                      	 
      	
                        PM

                      	 
	
                        IND
      Safety alert reporting to sites

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        0.75

                      	 
      	
                        13

                      	 
      	
                        9.75

                      	 
      	
                        PM

                      	 
	
                        Annual
      re-approval documentation

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        1

                      	 
      	
                        20

                      	 
      	
                        20

                      	 
      	
                        PM

                      	 
	
                        Study/site
      closure documentation

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        2

                      	 
      	
                        20

                      	 
      	
                        40

                      	 
      	
                        PM

                      	 
	
                        IRB
      payment facilitation

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        0.5

                      	 
      	
                        20

                      	 
      	
                        10

                      	 
      	
                        PM

                      	 
	
                        IRB
      payment

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 
      	 
      	 
      	
                        0.5

                      	 
      	
                        20

                      	 
      	
                        10

                      	 
      	
                        PM

                      	 
	
                        CRA

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Training
      – protocol, project & therapy area

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Initial
      CRA training

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        Periodic
      CRA training (i.e. amendments, forms, SOPs, other new
      information)

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        4

                      	 
      	
                        32

                      	 
      	
                        CRA

                      	 
	
                        Team
      Teleconference

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	
                        0.8

                      	 
      	
                        296

                      	 
      	
                        222

                      	 
      	
                        CRA

                      	 
	
                        Site
      Selection Visits

                      	 
      	 
      	 
      	
                        N/A

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 


              

            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 19
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO
      Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version
      Date:

              	
                16DEC2008

              	
                Work
      Order #:

              	
                WO4

              


      

    

    


    
      
        
          
            
              
                	
                        Contact
      sites and confirm date for visit

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Send
      confirmation letter

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Interview
      PI and site staff regarding experience

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      project requirements and expectations

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Tour
      facility and assess site

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Prepare
      report and make recommendation of site suitability

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Prep

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        1

                      	 
      	
                        1

                      	 
      	
                        1

                      	 
      	
                        CRA

                      	 
	
                        Travel

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        CRA

                      	 
	
                        On-Site

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        3

                      	 
      	
                        1

                      	 
      	
                        3

                      	 
      	
                        CRA

                      	 
	
                        Report
      Writing and Follow-up

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        5

                      	 
      	
                        1

                      	 
      	
                        5

                      	 
      	
                        CRA

                      	 
	
                        Total

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        17

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        CAA

                      	 
	
                        Site
      Initiation Visit

                      	 
      	 
      	 
      	
                        X

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Contact
      sites and confirm date for visit and provide an agenda

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Send
      confirmation letter

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Complete
      Monitors’ Sign-in Log

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      regulatory documentation

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      Study protocol and CRF including:

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Inclusion/exclusion
      criteria

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Efficacy
      parameters and measurement

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Study
      schedule

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Complete/evaluable
      patient definitions

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Study
      medication procedures

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Lab
      requirements

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        CRF
      completion instructions

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      adverse event reporting, including:

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Definition
      of AEs and SAEs

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Requirements
      for documentation collection

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Proper
      procedures for reporting SAEs to Sponsor and REB

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Follow-up
      requirements

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      Investigational Brochure

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      communication channels

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      requirements for source documentation

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        IRB/site
      responsibilities

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      monitoring schedule

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      study site documentation

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Train
      study coordinators

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      PI contract and payment schedule

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Prepare
      study initiation visit report

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 


              

            

          

        

      

    

    


    CONFIDENTIAL


      
        

      

    

    Page 20
of 36

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

    


    
      
        
          
            
              
                
                  
                    
                      
                        	
                                Send site
      SIV report and ackg. Form

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Prep

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                1

                              	 
      	
                                1

                              	 
      	
                                1

                              	 
      	
                                CRA

                              	 
	
                                Travel

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                8

                              	 
      	
                                1

                              	 
      	
                                8

                              	 
      	
                                CRA

                              	 
	
                                On-Site

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                5

                              	 
      	
                                1

                              	 
      	
                                5

                              	 
      	
                                CRA

                              	 
	
                                Report
      Writing and Follow-up

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                5

                              	 
      	
                                1

                              	 
      	
                                5

                              	 
      	
                                CRA

                              	 
	
                                Sub-Total/site

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                                19

                              	 
      	
                                CRA

                              	 
	
                                Total

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                19

                              	 
      	
                                20

                              	 
      	
                                380

                              	 
      	
                                CRA

                              	 
	
                                Interim
      Monitoring

                              	 
      	 
      	 
      	
                                X

                              	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Send
      confirmation letter

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Complete
      Monitors’ Sign-in Log

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Verify
      proper Informed Consent procedures

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Monitor
      in accordance with protocol/ICH/GCP

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                100%
      source document verification vs. CRF

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Assess
      patient eligibility (protocol inclusion/exclusion/randomization
      criteria)

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Provide
      site with written query records to be retained with each
    CRF

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Review
      study-related regulatory documents

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Review
      monitoring & discrepancy report queries

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Source
      verify data clarification/correction forms

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Review
      of laboratory data

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Review
      and verify SAEs (100% SDV)

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Verify
      study drug inventory and storage

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Verify
      proper accountability and destruction of IP and study supplies per
      protocol

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Maintain
      protocol violation list

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Monitoring
      of other variables as specified

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Prepare
      monitoring visit reports following each monitoring visit

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Provide
      monitoring follow-up reports to sites following each visit

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Regulator
      contacts with sites & TC reports

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Ongoing
      training of site personnel

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                CRF
      and query management

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                                Prep

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                2

                              	 
      	
                                1

                              	 
      	
                                2

                              	 
      	
                                CRA

                              	 
	
                                Travel

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                8

                              	 
      	
                                1

                              	 
      	
                                8

                              	 
      	
                                CRA

                              	 
	
                                On-Site

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                8

                              	 
      	
                                1

                              	 
      	
                                8

                              	 
      	
                                CRA

                              	 
	
                                Report
      Writing and Follow-up

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                5

                              	 
      	
                                1

                              	 
      	
                                5

                              	 
      	
                                CRA

                              	 
	
                                Sub-Total/site

                              	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                                23

                              	 
      	
                                CRA

                              	 
	
                                Total

                              	 
      	 
      	 
      	 
      	 	 	 
      	
                                23

                              	 
      	
                                258

                              	 
      	
                                5925

                              	 
      	
                                CRA

                              	 
	
                                Un-Blinded
      CRA

                              	
                                  

                              	
                                N/A

                              	
                                  

                              	 
      	 	 	
                                  

                              	 
      	
                                  

                              	 
      	
                                  

                              	 
      	
                                  

                              	 
      	 


                      

                    

                  

                

              

            

          

        

      

    

    


    CONFIDENTIAL 

    
      

    

    Page 21 of 36


    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

     

    
      
        
          	
                  MSA#:

                	
                  YMB07-MSA-17MAY2007

                	
                  WO Version Code:

                	
                  YMB08-WO4-15DEC2008-3.0

                
	
                  Version Date:

                	
                  16DEC2008

                	
                  Work Order #:

                	
                  WO4

                


        

      

       

    

    
      
        
          
            
              
                
                  	
                          Close
      Out Visit

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          COV
      within 6 weeks post data base lock

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Contact
      potential sites, confirm data for visit

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Send
      confirmation letter

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Complete
      Monitors’ Sign-in Log

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Ensure
      site regulatory documentation is complete and accessible future
      audits

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Ensure
      that the investigator is aware of his/her responsibilities

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Financial
      Disclosure documentation

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Ensure
      that any remaining clinical trial material is removed from the study
      site

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Prepare
      COV report following visit

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Provide
      follow-up report to sites

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Follow-up
      with sites to resolve open issues

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Prep

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          2

                        	 
      	
                          1

                        	 
      	
                          2

                        	 
      	
                          CRA

                        	 
	
                          Travel

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          CRA

                        	 
	
                          On-Site

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          CRA

                        	 
	
                          Report
      Writing and Follow-up

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          5

                        	 
      	
                          1

                        	 
      	
                          5

                        	 
      	
                          CRA

                        	 
	
                          Sub-Total/site

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                          23

                        	 
      	
                          CRA

                        	 
	
                          Total

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          23

                        	 
      	
                          20

                        	 
      	
                          460

                        	 
      	
                          CRA

                        	 
	
                          Site
      Management/Interaction (1hr/site/week)

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          10

                        	 
      	
                          134

                        	 
      	
                          1340

                        	 
      	
                          CRA

                        	 
	
                          Lead
      CRA

                        	 
      	
                          N/A

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Overall
      Project Management

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Training
      – protocol, project & therapy area

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Initial
      PM training

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          12

                        	 
      	
                          1

                        	 
      	
                          12

                        	 
      	
                          PM

                        	 
	
                          Periodic
      PM training

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          In-house
      study management

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Selection
      – CDN site

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          Feasibility
      from admin

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          Confidential
      Disc. Agreement

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          CDA
      approval

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          CRTRA
      template

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          CTRA
      template approval

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          CTRA
      negotiation

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          CTRA
      site sign off

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                          PM

                        	 
	
                          Preparation
      of initial project specific reg pkg

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Review
      received reg docs:

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          site
      – QUI

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          0.25

                        	 
      	
                          20

                        	 
      	
                          5

                        	 
      	
                          PM

                        	 
	
                          REBA

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          0.25

                        	 
      	
                          20

                        	 
      	
                          5

                        	 
      	
                          PM

                        	 
	
                          CTSI

                        	
                            

                        	 
      	
                            

                        	
                          X

                        	 	 	
                            

                        	
                          0.25

                        	
                            

                        	
                          20

                        	
                            

                        	
                          5

                        	
                            

                        	
                          PM

                        	 


                

              

            

          

        

      

    

     

    CONFIDENTIAL 

    
      

    

    Page 22 of 36
 

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     

    
      
        
          
            
              
                
                  
                    	
                            Consent
      to Use Personal Data

                          	 
      	 
      	 
      	
                            N/A

                          	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Protocol
      signature page

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.25

                          	 
      	
                            20

                          	 
      	
                            5

                          	 
      	
                            PM

                          	 
	
                            Financial
      Disclosure

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.25

                          	 
      	
                            20

                          	 
      	
                            5

                          	 
      	
                            PM

                          	 
	
                            CV

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.25

                          	 
      	
                            20

                          	 
      	
                            5

                          	 
      	
                            PM

                          	 
	
                            MD
      qualification

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.25

                          	 
      	
                            20

                          	 
      	
                            5

                          	 
      	
                            PM

                          	 
	
                            Internal
      project team meetings – biweekly

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            74

                          	 
      	
                            74

                          	 
      	
                            PM

                          	 
	
                            Site
      level management

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            8

                          	 
      	
                            20

                          	 
      	
                            160

                          	 
      	
                            PM

                          	 
	
                            Weekly
      Regular status reports for client

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            148

                          	 
      	
                            148

                          	 
      	
                            PM

                          	 
	
                            Liaise
      weekly with sponsor

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            148

                          	 
      	
                            148

                          	 
      	
                            PM

                          	 
	
                            TMF
      set-up and maintenance oversight

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            8

                          	 
      	
                            1

                          	 
      	
                            8

                          	 
      	
                            PM

                          	 
	
                            Site
      budge set-up

                          	 
      	
                            X

                          	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Payment
      calculation (quarterly)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            206

                          	 
      	
                            206

                          	 
      	
                            PM

                          	 
	
                            Payment
      tracking

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.5

                          	 
      	
                            205

                          	 
      	
                            103

                          	 
      	
                            PM

                          	 
	
                            Payment
      issuance

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            0.25

                          	 
      	
                            206

                          	 
      	
                            51.5

                          	 
      	
                            PM

                          	 
	
                            SOPs
      assignment documentation

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            3

                          	 
      	
                            1

                          	 
      	
                            3

                          	 
      	
                            PM

                          	 
	
                            Responsibility
      assignment

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            PM

                          	 
	
                            Preparation
      of Project Plan (1 review)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            8

                          	 
      	
                            1

                          	 
      	
                            8

                          	 
      	
                            PM

                          	 
	
                            Preparation
      of Monitoring Plan (1 review)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            8

                          	 
      	
                            1

                          	 
      	
                            8

                          	 
      	
                            PM

                          	 
	
                            Preparation
      of Visit Booklet (1 review)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            12

                          	 
      	
                            1

                          	 
      	
                            12

                          	 
      	
                            PM

                          	 
	
                            Development
      of Pharmacy Manual (1 review)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            12

                          	 
      	
                            1

                          	 
      	
                            12

                          	 
      	
                            PM

                          	 
	
                            Development
      of SAE Plan

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            16

                          	 
      	
                            1

                          	 
      	
                            16

                          	 
      	
                            PM

                          	 
	
                            Development
      of Recruitment Plan

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            12

                          	 
      	
                            1

                          	 
      	
                            12

                          	 
      	
                            PM

                          	 
	
                            Review
      of Monitoring Trip Reports

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            258

                          	 
      	
                            258

                          	 
      	
                            PM

                          	 
	
                            Prep.
      Of Study specific forms

                          	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Prep.
      Study specific tracking tools

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            12

                          	 
      	
                            1

                          	 
      	
                            12

                          	 
      	
                            PM

                          	 
	
                            QoL,
      questionnaires and/or patient diaries, patient (alert)
    cards)

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            12

                          	 
      	
                            1

                          	 
      	
                            12

                          	 
      	
                            PM

                          	 
	
                            Drug
      Accountability Form

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            4

                          	 
      	
                            1

                          	 
      	
                            4

                          	 
      	
                            PM

                          	 
	
                            Individual
      Subject Drug logs

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            4

                          	 
      	
                            1

                          	 
      	
                            4

                          	 
      	
                            PM

                          	 
	
                            Drug
      Return & Reconciliation Form

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            4

                          	 
      	
                            1

                          	 
      	
                            4

                          	 
      	
                            PM

                          	 
	
                            Clinical
      Re-supplies Form

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            PM

                          	 
	
                            Drug
      Receipt Form

                          	 
      	
                            X

                          	 
      	
                            X

                          	 	 	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            PM

                          	 
	
                            Release
      of IP (RIP) Form

                          	 
      	
                            X

                          	 
      	
                            (X)

                          	 	 	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            PM

                          	 
	
                            Destruction
      of IP (DIP) Form

                          	 
      	 
      	 
      	
                            (X)

                          	 	 	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            1

                          	 
      	
                            PM

                          	 
	
                            Study
      specific tracking tools

                          	 
      	 
      	 
      	
                            X

                          	 	 	 
      	
                            8

                          	 
      	
                            1

                          	 
      	
                            8

                          	 
      	
                            PM

                          	 
	
                            Investigational
      Product (IP) and other Clinical Study Supplies

                          	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Labeling,
      coding and packing of IP (including provision of sample
      labels)

                          	 
      	
                            X

                          	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Comparator
      Procurement

                          	 
      	
                            X

                          	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                            Preparation
      of written instructions for handling and storage of IP

                          	
                              

                          	
                            X

                          	
                              

                          	 
      	 	 	
                              

                          	 
      	
                              

                          	 
      	
                              

                          	 
      	
                              

                          	 
      	 


                  

                

              

            

          

        

      

    

    
       


      CONFIDENTIAL 

      
        

      

      Page 23 of 36

         

      
        
          
             


          

          
            
            

            
              

            

          

          
             


          

        

      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     

    
      
        
          
            
              
                
                  	
                          Request
      for import/export approvals for IP

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Preparation
      of custom clearance(s)

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Storage
      of IP oversight

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Request
      for authorization to release IP oversight

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Authorization
      to distribute drug

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Packaging/labelling
      of Clinical Supplies Oversight

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Distribution
      of Clinical Study Supplies to sites

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Tracking
      of IP

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Tracking
      of Clinical Study Supplies

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Organization
      of destruction of unused Clinical Study Supplies

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          12

                        	 
      	
                          1

                        	 
      	
                          12

                        	 
      	
                          PM

                        	 
	
                          Study
      Completion/Study Termination

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Notification
      to national/local authorities of study termination

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Final
      recon of TMF

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Archiving
      of Sponsor’s TMF

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          PM
      – Pre-Study/Specific Task Sub-Total

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                          1383.5

                        	 
      	
                          PM

                        	 
	
                          Local
      Management Sub-Total (est. hours/week x # wks)

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          10

                        	 
      	
                          134

                        	 
      	
                          1340

                        	 
      	
                          PM

                        	 
	
                          Ex-house
      Project Management

                        	 
      	
                          X

                        	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Co-Initiation/Monitoring/COV

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Prep

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          1

                        	 
      	
                          1

                        	 
      	
                          1

                        	 
      	
                          PM

                        	 
	
                          Travel

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          12

                        	 
      	
                          1

                        	 
      	
                          12

                        	 
      	
                          PM

                        	 
	
                          On-Site
      (average)

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Admin

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          3

                        	 
      	
                          1

                        	 
      	
                          3

                        	 
      	
                          PM

                        	 
	
                          Sub-Total/site

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                          24

                        	 
      	
                          PM

                        	 
	
                          Total

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          24

                        	 
      	
                          4

                        	 
      	
                          96

                        	 
      	
                          PM

                        	 
	
                          Ad
      hoc meetings

                        	 
      	 
      	 
      	
                          X

                        	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Prep

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          1

                        	 
      	
                          1

                        	 
      	
                          1

                        	 
      	
                          PM

                        	 
	
                          Travel

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          12

                        	 
      	
                          1

                        	 
      	
                          12

                        	 
      	
                          PM

                        	 
	
                          On-Site
      (average)

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          8

                        	 
      	
                          1

                        	 
      	
                          8

                        	 
      	
                          PM

                        	 
	
                          Admin

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          3

                        	 
      	
                          1

                        	 
      	
                          3

                        	 
      	
                          PM

                        	 
	
                          Sub-Total/Mtg

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	
                          24

                        	 
      	
                          PM

                        	 
	
                          Total

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          245

                        	 
      	
                          12

                        	 
      	
                          288

                        	 
      	
                          PM

                        	 
	
                          Administration
      – COA & Document Management

                        	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Start
      Up Documentation Activities

                        	 
      	
                          (X)

                        	 
      	
                          X

                        	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                          Assemble
      site reg. packages

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          1.25

                        	 
      	
                          20

                        	 
      	
                          25

                        	 
      	
                          COA

                        	 
	
                          Courier
      packages to sites

                        	 
      	 
      	 
      	 
      	 	 	 
      	
                          0.25

                        	 
      	
                          20

                        	 
      	
                          5

                        	 
      	
                          COA

                        	 
	
                          Initial
      review of Regulatory Documents

                        	
                            

                        	 
      	
                            

                        	 
      	 	 	
                            

                        	
                          1.5

                        	
                            

                        	
                          20

                        	
                            

                        	
                          30

                        	
                            

                        	
                          COA

                        	 


                

              

            

          

        

      

    

    
       


      CONFIDENTIAL 

      
        

      

      Page 24 of 36

       

      
        
          
             


          

          
            
            

            
              

            

          

          
             


          

        

      

    

    
      


      
        
          	
                  MSA#:

                	
                  YMB07-MSA-17MAY2007

                	
                  WO Version Code:

                	
                  YMB08-WO4-15DEC2008-3.0

                
	
                  Version Date:

                	
                  16DEC2008

                	
                  Work Order #:

                	
                  WO4

                


        

      

       

    

    
      
        
          
            
              
                	
                        Receive,
      log, scan & file initial reg docs

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        1.5

                      	 
      	
                        20

                      	 
      	
                        30

                      	 
      	
                        COA

                      	 
	
                        Follow-up
      on reg doc errors & omissions

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.5

                      	 
      	
                        15

                      	 
      	
                        7.5

                      	 
      	
                        COA

                      	 
	
                        Courier
      – second round

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.25

                      	 
      	
                        15

                      	 
      	
                        3.75

                      	 
      	
                        COA

                      	 
	
                        Second
      review of regulatory documents

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        15

                      	 
      	
                        7.5

                      	 
      	
                        COA

                      	 
	
                        Receive,
      log, scan & file 2nd
      round reg docs

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        15

                      	 
      	
                        15

                      	 
      	
                        COA

                      	 
	
                        Identify
      Table of Contents for ISF/IHF/GSF

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        1

                      	 
      	
                        1

                      	 
      	
                        COA

                      	 
	
                        Assemple
      PI Site Files (ISF) for TMF

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        20

                      	 
      	
                        30

                      	 
      	
                        COA

                      	 
	
                        Courier
      site ISF to PI

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        20

                      	 
      	
                        5

                      	 
      	
                        COA

                      	 
	
                        Assemble
      In-House site File (IHF) (GSF) for TMF

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        20

                      	 
      	
                        20

                      	 
      	
                        COA

                      	 
	
                        Crease
      eTMF folders

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        COA

                      	 
	
                        CRF
      related admin

                      	 
      	 
      	 
      	
                        N/A

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        CDA
      – send to sites; review; send to Client

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        CTRA
      – send to sites; review; send to Client

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        General
      Admin

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Post
      tracking tools to web for client

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Assist
      with IRB/reg. authority submissions

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Ongoing
      regulatory doc. tracking /scanning

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Contact
      sites for enrolment updates

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        High
      level site support

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Assist
      with query resolution

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        TC
      minutes

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        COA
      General Admin Total

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        15

                      	 
      	
                        148

                      	 
      	
                        2220

                      	 
      	
                        COA

                      	 
	
                        General
      –TMF (Document Management)

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Document
      receipt & sorting

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Document
      review for completeness

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Management
      of deficiencies

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Scanning
      & hard copy filing

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        e-naming
      & e-filing

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Maintenance
      of document tracking tool

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Ongoing
      review of TMF for completeness

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Ongoing
      document retrieval and re-filing

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Fax,
      email or courier docs to CRAs/Sponsor

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Return
      of Sponsor’s TMF

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Document
      Management General TMF Total (hrs/week)

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        10

                      	 
      	
                        148

                      	 
      	
                        1480

                      	 
      	
                        DOC

                      	 
	
                        Allphase
      Center of Excellence (ACE) Training

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Medical
      Writing

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Quality
      Assurance

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Familiarization
      with client SOPs (if applicable)

                      	
                          

                      	 
      	
                          

                      	
                        X

                      	 	 	
                          

                      	 
      	
                          

                      	 
      	
                          

                      	 
      	
                          

                      	 
      	 


              

            

          

        

      

    

     

    
      CONFIDENTIAL 

      
        

      

      Page 25 of 36

       

      
        
          
             


          

          
            
            

            
              

            

          

          
             


          

        

      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     

    
      
        
          
            
              
                	
                        Familiarization
      with protocol

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Inspection
      of site regulatory files

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      and assessment of site SOPs

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Random
      sampling of source & CRF data

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Discussion
      with site personnel re: processes and findings

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Inspection
      of client TMF regulatory files

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      of vendor facilities, SOPs, processes

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Discussion
      with vendor personnel re: processes and findings

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Preparation
      of audit report

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Follow-up
      resolutions

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Vendor
      Audits

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Site
      Audits

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Prep

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Travel

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        12

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        On-Site

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        16

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Admin/Report
      Writing

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        12

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Sub-Total

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        48

                      	 
      	
                        3

                      	 
      	
                        144

                      	 
      	
                        QA

                      	 
	
                        TMF
      Audit

                      	 
      	 
      	 
      	
                        N/A

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Prep

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Travel

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        On-Site

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        32

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Admin/Report
      Writing

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        12

                      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Sub-Total

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        60

                      	 
      	
                        0

                      	 
      	
                        0

                      	 
      	
                        QA

                      	 
	
                        Safety

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Overall
      Medical Oversight

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        24/7
      coverage

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.25

                      	 
      	
                        134

                      	 
      	
                        33.5

                      	 
      	
                        MM

                      	 
	
                        Consultation
      with sites

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.25

                      	 
      	
                        128

                      	 
      	
                        32

                      	 
      	
                        MM

                      	 
	
                        Consultation
      with Client

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        1

                      	 
      	
                        11

                      	 
      	
                        11

                      	 
      	
                        MM

                      	 
	
                        Protocol
      deviation decision making and management (as required)

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.75

                      	 
      	
                        13

                      	 
      	
                        9.75

                      	 
      	
                        MM

                      	 
	
                        SAE
      Trend Analysis

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        MM

                      	 
	
                        Lab
      alert review

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        1

                      	 
      	
                        6

                      	 
      	
                        6

                      	 
      	
                        MM

                      	 
	
                        Protocol
      deviation processing and tracking

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.75

                      	 
      	
                        128

                      	 
      	
                        96

                      	 
      	
                        PM

                      	 
	
                        AE/SAE
      Database Setup

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        SAE
      Collection, Processing & Reporting

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Review
      of SAE Plan

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        4

                      	 
      	
                        1

                      	 
      	
                        4

                      	 
      	
                        MM

                      	 
	
                        SAE
      report receipt, processing & follow-up

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        3

                      	 
      	
                        64

                      	 
      	
                        192

                      	 
      	
                        DS

                      	 
	
                        CIOMs
      generation

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        3

                      	 
      	
                        13

                      	 
      	
                        39

                      	 
      	
                        DS

                      	 
	
                        Submit
      Alert Reports to Reg. Agencies/IRB/Sponsor

                      	
                          

                      	 
      	
                          

                      	 
      	 	 	
                          

                      	
                        2

                      	
                          

                      	
                        13

                      	
                          

                      	
                        39

                      	
                          

                      	
                        DS

                      	 


              

            

          

        

      

    

    
       


      CONFIDENTIAL 

      
        

      

      Page 26 of 36

       

      
        
          
             


          

          
            
            

            
              

            

          

          
             


          

        

      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     

    
      
        
          
            
              
                	
                        Submit
      SAE Reports to Sites

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        1.5

                      	 
      	
                        13

                      	 
      	
                        26

                      	 
      	
                        DS

                      	 
	
                        Annual
      safety reporting

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        16

                      	 
      	
                        3

                      	 
      	
                        19.5

                      	 
      	
                        PM

                      	 
	
                        Teleconferences
      with Sponsor

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        2

                      	 
      	
                        11

                      	 
      	
                        48

                      	 
      	
                        MM

                      	 
	
                        SAE
      Medical Evaluation

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	
                        22

                      	 
      	
                        MM

                      	 
	
                        SAE
      review of report & supporting info

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.75

                      	 
      	
                        64

                      	 
      	
                        48

                      	 
      	
                        MM

                      	 
	
                        SAE
      Narrative

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        0.75

                      	 
      	
                        64

                      	 
      	
                        48

                      	 
      	
                        MM

                      	 
	
                        Data
      Safety Monitoring Board

                      	 
      	 
      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Formation
      and Management

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Provide
      3 suitable board members (2MD; 1 Biostat) & facilitate (3) meetings by
      teleconference

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        24

                      	 
      	
                        1

                      	 
      	
                        24

                      	 
      	
                        PM

                      	 
	
                        Organize
      DSMB meetings

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        12

                      	 
      	
                        3

                      	 
      	
                        36

                      	 
      	
                        PM

                      	 
	
                        Interact
      with sponsor regarding conclusions

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	
                        3

                      	 
      	
                        24

                      	 
      	
                        PM

                      	 
	
                        Implement
      next steps

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	
                        3

                      	 
      	
                        24

                      	 
      	
                        PM

                      	 
	
                        Charter,
      SOPs, Meeting #1

                      	 
      	
                        (X)

                      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Creation
      of draft & final SOP, Charter, Open & Closed Report format;
      provide support/advice for creating DSMB and defining its duties &
      responsibilities for the project

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        24

                      	 
      	
                        1

                      	 
      	
                        24

                      	 
      	
                        PM

                      	 
	
                        Meeting
      #1 (PM): discussion of protocol, procedures, role & functioning of
      DSMB

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        6

                      	 
      	
                        1

                      	 
      	
                        6

                      	 
      	
                        PM

                      	 
	
                        Meeting
      #1 (COA): Attendance & Minutes

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	
                        1

                      	 
      	
                        8

                      	 
      	
                        COA

                      	 
	
                        Meeting
      #1 (MM): discussion of protocol, procedures, role & functioning of
      DSMB

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        6

                      	 
      	
                        1

                      	 
      	
                        6

                      	 
      	
                        MM

                      	 
	
                        Meeting
      #1 (BIO): discussion of protocol, procedures, role & functioning of
      DSMB

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        BIO

                      	 
	
                        Administration

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Distribute
      meeting materials

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        2

                      	 
      	
                        3

                      	 
      	
                        6

                      	 
      	
                        COA

                      	 
	
                        MM:
      Review of protocol & related changes, SAP, minutes, reports,
      etc.

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        16

                      	 
      	
                        1

                      	 
      	
                        16

                      	 
      	
                        MM

                      	 
	
                        BIO:
      Review of protocol & related changes, SAP, minutes, reports,
      etc.

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        BIO

                      	 
	
                        Board
      Member Participation & Evaluation

                      	 
      	 
      	 
      	
                        X

                      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        MM x
      2: Meetings #2 (closed) & #3 (open) by teleconference

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        12

                      	 
      	
                        2

                      	 
      	
                        24

                      	 
      	
                        MM

                      	 
	
                        BIO:
      Meetings #2 (closed) & #3(open) by teleconference

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        BIO

                      	 
	
                        Preparation
      of Open & Closed minutes (non-CRO personnel)

                      	 
      	 
      	 
      	 
      	 	 	 
      	
                        8

                      	 
      	
                        2

                      	 
      	
                        16

                      	 
      	
                        COA

                      	 
	
                        BIO:
      preparation of Open & Closed reports

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        BIO

                      	 
	
                        DM:
      preparation of database extract for Open & Closed
    reports

                      	 
      	
                        X

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	
                        DM

                      	 
	
                        Data
      Management

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Biostatistical
      Services

                      	 
      	
                        N/A

                      	 
      	 
      	 	 	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
      	 
	
                        Data
      Management – Licenses and Fees

                      	
                          

                      	
                        N/A

                      	
                          

                      	 
      	 	 	
                          

                      	 
      	
                          

                      	 
      	
                          

                      	 
      	
                          

                      	 
      	 


              

            

          

        

      

    

    
       

      CONFIDENTIAL 

      
        

      

      Page 27 of 36

       

      
        
          
             


          

          
            
            

            
              

            

          

          
             


          

        

      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     


    6.
Estimate

     

    Based on
the information provided, we have prepared an estimate which we feel is
reasonable at this time. Please be assured that Allphase Clinical
Research strives to economize appropriately whenever possible. Based on the
preceding section of this proposal, the following labour costs have been
estimated, in Canadian dollars. Travel related expenses are to be reimbursed by
the client separately. Allphase reserves the right to revise this estimate if
the assumptions provided herein change. Once executed, revisions to this Work
Order will be documented using a Scope Change process. If the accumulated
Scope Change value exceeds 10% of the estimated labour total, a Change
Order will be processed.

    


    6
a. Summary – Client Template

    


    
      
        	
                YM
      BioSciences Inc.

              	
                  

              	
                5045
      Orbitor Drive, Building 11, Suite 400

                Mississauga,
      Ontario, Canada L4W 4Y4

                Telephone:
      905.629.9761

                Facsimile:
      905.629.4959

                Website:
      www.ymbiosciences.com

              


      

    

    


    CRO-Estimated Project Cost
Outline

    Executive
Summary

    


    CRO Name: Allphase Clinical
Research Inc.

    Project: Palliative
Radiotherapy

    Date: 10DEC2008

    


    
      
        
          
            
              	
                      Project
      Start-up/Initiation:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      CRF
      Design

                    	 	
                      Included
      under DM estimate

                    	 
	 
      	 	 	 
	
                      Grant
      Payment Administration

                    	 	 	36,050.00	 
	 
      	 	 	 	 
	
                      Critical
      Document Collection/TMF Set-up/QA/Site ID &
Feasibility

                    	 	 	21,381.25	 
	 
      	 	 	 	 
	
                      Monitoring
      Plan/CRA manual

                    	 	 	2,000.00	 
	 
      	 	 	 	 
	
                      Site
      Binders/Study Procedures (reference) Manual

                    	 	 	1,200.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	60,631.25	 


            

          

        

      

    

     

    
      
        
          
            
              	
                      Investigator
      Meeting:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      Investigator
      meeting set-up/Coordination

                    	 	 	12.575.00	 
	 
      	 	 	 	 
	
                      Investigator
      meeting preparation/Attendance

                    	 	 	18,710.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	31,285.00	 


            

          

        

      

    

    
       


      CONFIDENTIAL 

      
        

      

      Page 28 of 36

       

    

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    
      


      
        
          	
                  MSA#:

                	
                  YMB07-MSA-17MAY2007

                	
                  WO Version Code:

                	
                  YMB08-WO4-15DEC2008-3.0

                
	
                  Version Date:

                	
                  16DEC2008

                	
                  Work Order #:

                	
                  WO4

                


        

      

         

    

    
      
        
          
            
              	
                      Clinical
      Site Monitoring and Site Management:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      Project
      team training/Familiarization

                    	 	 	10,380.00	 
	 
      	 	 	 	 
	
                      Site
      Selection Visits

                    	 	 	0.00	 
	 
      	 	 	 	 
	
                      Site
      Initiation Visits

                    	 	 	34,200.00	 
	 
      	 	 	 	 
	
                      Interim
      Site Monitoring Visits

                    	 	 	533,232.00	 
	 
      	 	 	 	 
	
                      Interim
      Site Monitoring Visits (follow-up)

                    	 	
                      included
      in above

                    	 
	 
      	 	 	 	 
	
                      Site
      Close-out Visits

                    	 	 	41,400.00	 
	 
      	 	 	 	 
	
                      Site
      Interaction (Telephone Contact)

                    	 	 	120,600.00	 
	 
      	 	 	 	 
	
                      Query
      Management

                    	 	
                      included
      in site visits

                    	 
	 
      	 	 	 	 
	
                      Essential
      Document/Site file Maintenance

                    	 	
                      included
      in site visits

                    	 
	 
      	 	 	 	 
	
                      Trial
      Master File reconciliations

                    	 	
                      included
      in site visits

                    	 
	 
      	 	 	 	 
	
                      Clinical
      Monitoring Oversight (PM)

                    	 	 	25,800.00	 
	 
      	 	 	 	 
	
                      Project
      Kick-off meeting

                    	 	 	7,160.00	 
	 
      	 	 	 	 
	
                      Mid-Study
      project team meeting

                    	 	 	7,160.00	 
	 
      	 	 	 	 
	
                      Teleconferences
      with YM BioSciences

                    	 	 	34,780.00	 
	 
      	 	 	 	 
	
                      Internal
      Team Meetings

                    	 	 	7,400.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	822,112.00	 


            

          

        

      

    

     

    
      
        
          
            
              	
                      Medical
      Management:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      Project
      Team training/Familiarization

                    	 	 	1,400.00	 
	 
      	 	 	 	 
	
                      Medical
      Monitoring (includes DSMB involvement)

                    	 	 	60,787.50	 
	 
      	 	 	 	 
	
                      Review
      of AE Coding

                    	 	
                      included
      under DM estimate

                    	 
	 
      	 	 	 	 
	
                      Annual
      Safety Reporting

                    	 	 	16,800.00	 
	 
      	 	 	 	 
	
                      Project
      Kick-off meeting

                    	 	 	2,450.00	 
	 
      	 	 	 	 
	
                      Teleconferences
      with YM BioSciences

                    	 	 	7,700.00	 
	 
      	 	 	 	 
	
                      Internal
      Team meetings

                    	 	 	2,450.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	91,588.00	 


            

          

        

      

    

     


    CONFIDENTIAL 

    
      

    

    Page 29 of 36

     

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    
      


      
        
          	
                  MSA#:

                	
                  YMB07-MSA-17MAY2007

                	
                  WO Version Code:

                	
                  YMB08-WO4-15DEC2008-3.0

                
	
                  Version Date:

                	
                  16DEC2008

                	
                  Work Order #:

                	
                  WO4

                


        

      

       

    

    
      
        
          
            
              	
                      Pharmacovigilance:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      Project
      Team Training/Familiarization

                    	 	
                      included
      in Med Mgmt above

                    	 
	 
      	 	 	 
	
                      Create
      SAE Management Plan

                    	 	 	3,000.00	 
	 
      	 	 	 	 
	
                      SAE
      Processing

                    	 	 	40,550.00	 
	 
      	 	 	 	 
	
                      Safety
      Narratives Writing

                    	 	 	20,700.00	 
	 
      	 	 	 	 
	
                      SAE
      Reconciliation

                    	 	
                      included
      in Med Mgmt above

                    	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	64,250.00	 


            

          

        

      

    

     

    
      
        
          
            
              	
                      Quality
      Assurance Site Audits:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      QA
      Site Audits

                    	 	 	14,400.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	14,400.00	 


            

          

        

      

    

     

    
      
        
          
            
              	
                      Project
      Management and Administrative Support:

                    	 	
                      Cost

                    	 
	 
      	 	 	 
	
                      Project
      Management and Support

                    	 	 	414,725.00	 
	 
      	 	 	 	 
	
                      Regulatory
      Document/Site File Maintenance

                    	 	 	111,000.00	 
	 
      	 	 	 	 
	
                      Sub-Total:

                    	 	$	525,735.00	 


            

          

        

      

    

     

    
      
        
          
            
              	
                      Total
      Labour:

                    	 	$	1,609,991.25	 
	 
      	 	 	 	 
	
                      Pass-Through
      Expenses:

                    	 	$	352,341.00	 
	 
      	 	 	 	 
	
                      ACTUAL
      TOTAL ESTIMATED PROJECT COST:

                    	 	$	1,962,332.25	 


            

          

        

      

    

     


    CONFIDENTIAL 

    
      

    

    Page 30 of 36

     

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

     

    6
b. Summary – Allphase Template

    


    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  
                                    
                                      
                                        
                                          
                                            
                                              	
                                                      Service

                                                    	 	
                                                      Resp.

                                                    	 	
                                                      Approx.

                                                      # hours

                                                    	 	 	
                                                      Hourly

                                                      Rate

                                                    	 	 	
                                                      TOTALS

                                                    	 
	
                                                      Project
      Management (PM)

                                                    	 
	
                                                      Pre-Study
      Activities

                                                    	 	
                                                      PM

                                                    	 	 	1,426	 	 	$	100	 	 	$	142,500	 
	
                                                      Local
      Investigator’s Meeting

                                                    	 	
                                                      PM

                                                    	 	 	97	 	 	$	100	 	 	$	9,700	 
	
                                                      Ethics

                                                    	 	
                                                      PM

                                                    	 	 	173.75	 	 	$	100	 	 	$	17,375	 
	
                                                      Co-Initiation/IMV/COV

                                                    	 	
                                                      PM

                                                    	 	 	96	 	 	$	100	 	 	$	9,600	 
	
                                                      Ad
      hoc meetings

                                                    	 	
                                                      PM

                                                    	 	 	288	 	 	$	100	 	 	$	28,800	 
	
                                                      Safety
      - SAE

                                                    	 	
                                                      PM

                                                    	 	 	116	 	 	$	100	 	 	$	11,550	 
	
                                                      Safety
      – DSMB

                                                    	 	
                                                      PM

                                                    	 	 	138	 	 	$	100	 	 	$	13,800	 
	
                                                      Local
      Management

                                                    	 	
                                                      PM

                                                    	 	 	1,340	 	 	$	100	 	 	$	134,000	 
	
                                                      Sub-Total

                                                    	 	
                                                      PM

                                                    	 	 	3,674	 	 	$	100	 	 	$	367,375	 
	
                                                      Scientific
      Affairs

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Pre-Study
      Activities

                                                    	 	
                                                      DIR

                                                    	 	 	4	 	 	$	120	 	 	$	480	 
	
                                                      Sub-Total

                                                    	 	
                                                      DIR

                                                    	 	 	4	 	 	$	120	 	 	$	480	 
	
                                                      Clinical
      Monitoring (CRA)

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Pre-Study
      Activities

                                                    	 	
                                                      CRA

                                                    	 	 	144	 	 	$	90	 	 	$	12,960	 
	
                                                      Local
      Investigator’s Meeting

                                                    	 	
                                                      CRA

                                                    	 	 	104	 	 	$	90	 	 	$	9,360	 
	
                                                      Teleconferences

                                                    	 	
                                                      CRA

                                                    	 	 	222	 	 	$	90	 	 	$	19,980	 
	
                                                      Training

                                                    	 	
                                                      CRA

                                                    	 	 	64	 	 	$	90	 	 	$	5,760	 
	
                                                      Site
      Selection Visits

                                                    	 	
                                                      CRA

                                                    	 	 	0	 	 	$	90	 	 	$	0	 
	
                                                      Initiation
      Visits

                                                    	 	
                                                      CRA

                                                    	 	 	380	 	 	$	90	 	 	$	34,200	 
	
                                                      Interim
      Monitoring

                                                    	 	
                                                      CRA

                                                    	 	 	5925	 	 	$	90	 	 	$	533,232	 
	
                                                      Close-Out
      Visit

                                                    	 	
                                                      CRA

                                                    	 	 	460	 	 	$	90	 	 	$	41,400	 
	
                                                      Site
      Management/Interaction

                                                    	 	
                                                      CRA

                                                    	 	 	1340	 	 	$	90	 	 	$	120,600	 
	
                                                      Sub-Total

                                                    	 	
                                                      CRA

                                                    	 	 	8639	 	 	$	90	 	 	$	777,492	 
	
                                                      Clinical
      Operations Associate (COA)

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Pre-Study
      & Specific Tasks

                                                    	 	
                                                      COA

                                                    	 	 	208	 	 	$	75	 	 	$	15,581	 
	
                                                      Local
      Investigator’s Meeting

                                                    	 	
                                                      COA

                                                    	 	 	107	 	 	$	75	 	 	$	8,025	 
	
                                                      DSMB

                                                    	 	
                                                      COA

                                                    	 	 	30	 	 	$	75	 	 	$	2,250	 
	
                                                      General

                                                    	 	
                                                      COA

                                                    	 	 	2220	 	 	$	75	 	 	$	166,500	 
	
                                                      Sub-Total

                                                    	 	
                                                      COA

                                                    	 	 	2565	 	 	$	75	 	 	$	192,356	 
	
                                                      Document
      Management Associate (DOC)

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      General
      TMF Maintenance

                                                    	 	
                                                      DOC

                                                    	 	 	1480	 	 	$	75	 	 	$	111,000	 
	
                                                      Sub-Total

                                                    	 	
                                                      DOC

                                                    	 	 	1480	 	 	$	75	 	 	$	111,000	 
	
                                                      Quality
      Assurance (QA)

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Site
      Audits

                                                    	 	
                                                      QA

                                                    	 	 	144	 	 	$	100	 	 	$	14,400	 
	
                                                      TMF
      Audit

                                                    	 	
                                                      QA

                                                    	 	 	0	 	 	 	#100	 	 	$	0	 
	
                                                      Sub-Total

                                                    	 	
                                                      QA

                                                    	 	 	144	 	 	$	100	 	 	$	14,400	 
	
                                                      Drug
      Safety - Management

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Drug
      Safety

                                                    	 	
                                                      DS

                                                    	 	 	257	 	 	$	100	 	 	$	25,700	 
	
                                                      Sub-Total

                                                    	 	
                                                      DS

                                                    	 	 	257	 	 	$	100	 	 	$	25,700	 
	
                                                      Medical
      Monitoring

                                                    	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Pre-Study
      Activities

                                                    	 	
                                                      MM

                                                    	 	 	18	 	 	$	350	 	 	$	6,300	 
	
                                                      Local
      Investigator’s Meeting

                                                    	 	
                                                      MM

                                                    	 	 	12	 	 	$	350	 	 	$	4,200	 
	
                                                      Medical
      Monitoring

                                                    	 	
                                                      MM

                                                    	 	 	270	 	 	$	350	 	 	$	94,588	 
	
                                                      DSMB

                                                    	 	
                                                      MM

                                                    	 	 	46	 	 	$	350	 	 	$	16,100	 
	
                                                      Sub-Total

                                                    	 	
                                                      MM

                                                    	 	 	346	 	 	$	350	 	 	$	121,188	 
	
                                                      Estimated
      Project Operational – Sub-Total

                                                    	 	 	$	1,609,991	 
	 
      	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Estimated
      Project Pass-Through Costs – Sub-Total

                                                    	 	 	$	352,341	 
	 
      	 	 
      	 	 	 	 	 	 	 	 	 	 	 	 
	
                                                      Estimated
      Project - Total

                                                    	 	 	$	1,962,332	 
	
                                                      Estimated
      Project – Total/patient (Labour only)

                                                    	 	 	$	12,578	 
	
                                                      Estimated
      Project – Total/patient (Labour and pass-through)

                                                    	 	 	$	15,331	 


                                            

                                          

                                        

                                      

                                    

                                  

                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

     

    
      CONFIDENTIAL 

      
        

      

      Page 31 of 36

    

     

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

       

    7.
Estimated Pass-Through Expenses

     

    
      
        
          
            	 
      	 	 	 	 	 	 	 	
                    TOTALS
      (CDN)

                  	 	 	 	 
	
                    Pass-Through
      Expenses

                  	 	 	 	 	
                    Unit
      Cost

                  	 	 	
                    #
      Units

                  	 	 	
                    Total
      Cost

                  	 
	
                    Travel
      Expenses (1 Day Trip)

                  	 	 	75	%	 	 	200.00	 	 	 	276	 	 	$	55,200
      	 
	
                    Travel
      Expenses (2 Day Trip)

                  	 	 	25	%	 	 	800.00	 	 	 	92	 	 	$	73,600	 
	
                    Meal
      Expenses - day trip

                  	 	
                    per
      day

                  	 	 	 	30.00	 	 	 	276	 	 	$	8,280	 
	
                    Monitor
      Overnight Expenses (ie. Hotel)

                  	 	
                    per
      trip

                  	 	 	 	200.00	 	 	 	184	 	 	$	36,800	 
	
                    Meal
      Expenses - overnight

                  	 	
                    per
      trip

                  	 	 	 	60.00	 	 	 	184	 	 	$	11,040	 
	
                    Quality
      Assurance / Site Audit

                  	 	
                    per
      trip

                  	 	 	 	1,500.00	 	 	 	3	 	 	$	4,500	 
	
                    Allphase
      & Client Meeting Expenses

                  	 	
                    per
      person

                  	 	 	 	600.00	 	 	 	12	 	 	$	7,200	 
	
                    Miscellaneous
      Expenses (consumables* and communication costs) = $120 pp/month (active
      period)/CRA

                  	 	
                    per
      month

                  	 	 	 	120.00	 	 	 	125	 	 	$	15,000	 
	
                    Miscellaneous
      Expenses (consumables* and communication costs) = $120 pp/month for the
      entire study duration: 1PM & 1 COA

                  	 	
                    per
      month

                  	 	 	 	120.00	 	 	 	69	 	 	$	8,280	 
	
                    CRF
      Printing

                  	 	
                    per
      CRF

                  	 	 	 	50.00	 	 	 	0	 	 	$	0	 
	
                    Diaries
      in French and English

                  	 	 	 	 	 	
                    TBD

                  	 	 	 	 	 	 	 	 	 
	
                    Translation

                  	 	 	 	 	 	
                    TBD

                  	 	 	 	 	 	 	 	 	 
	
                    Teleconferences

                  	 	
                    per
      conf.

                  	 	 	 	25.00	 	 	 	74.00	 	 	$	1,850	 
	
                    Mailing

                  	 	
                    per
      letter

                  	 	 	 	2.00	 	 	 	408.00	 	 	$	816	 
	
                    Courier

                  	 	
                    per
      package

                  	 	 	 	25.00	 	 	 	148.00	 	 	$	3,700	 
	
                    Finance
      Couriers (expenses)

                  	 	
                    per
      package

                  	 	 	 	25.00	 	 	 	37.00	 	 	$	925	 
	
                    Newsletters

                  	 	
                    per
      newsletter

                  	 	 	 	2.00	 	 	 	0	 	 	$	0	 
	
                    TMF
      Regulatory Binders

                  	 	
                    per
      site

                  	 	 	 	50.00	 	 	 	20	 	 	$	1,000	 
	
                    Regulatory
      Binders

                  	 	
                    per
      site

                  	 	 	 	50.00	 	 	 	20	 	 	$	1,000	 
	
                    Study
      Reference Binders

                  	 	
                    per
      site

                  	 	 	 	50.00	 	 	 	20	 	 	$	1,000	 
	
                    Investigator
      Grants

                  	 	
                    per
      patient

                  	 	 	
                    TBD

                  	 	 	 	128	 	 	$	0	 
	
                    Ethics
      Committee/IRB Fees

                  	 	
                    per
      site

                  	 	 	
                    TBD

                  	 	 	 	0	 	 	 	 	 
	
                    Insurance

                  	 	
                    per
      site

                  	 	 	
                    TBD

                  	 	 	 	0	 	 	 	 	 
	
                    Advertising

                  	 	
                    per
      site

                  	 	 	
                    TBD

                  	 	 	 	0	 	 	 	 	 
	
                    Pharmacy
      Set up fees

                  	 	
                    per
      site

                  	 	 	
                    TBD

                  	 	 	 	0	 	 	 	 	 


          

        

      

    

    
       


      CONFIDENTIAL 

      
        

      

      Page 32 of 36

       

    

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    
      


      
        
          	
                  MSA#:

                	
                  YMB07-MSA-17MAY2007

                	
                  WO Version Code:

                	
                  YMB08-WO4-15DEC2008-3.0

                
	
                  Version Date:

                	
                  16DEC2008

                	
                  Work Order #:

                	
                  WO4

                


        

      

         

    

    
      
        
          
            
              
                
                  
                    	 
      	 	 
      	 	 	 	 	
                            Sub-Total:

                          	 	 	$	230,191	 
	
                            Local
      Investigator’s Meeting

                          	 	 
      	 	 	 	 	 	 	 	 	 	 
	
                            Investigator
      Meeting Airfare - site staff (PI business, CRC economy)

                          	 	
                            per
      site

                          	 	 	1,950.00	 	 	 	40	 	 	$	78,000	 
	
                            Investigator
      Meeting Airfare - Allphase staff (all economy)

                          	 	
                            per
      person

                          	 	 	900.00	 	 	 	3	 	 	$	2,700	 
	
                            Investigator
      Meeting Hotel - site staff (3 nights)

                          	 	
                            per
      person

                          	 	 	750.00	 	 	 	40	 	 	$	30,000	 
	
                            Investigator
      Meeting Hotel - Allphase staff (3 nights)

                          	 	
                            per
      person

                          	 	 	750.00	 	 	 	3	 	 	$	2,250	 
	
                            Transportation
      and meals

                          	 	
                            per
      person

                          	 	 	200.00	 	 	 	46	 	 	$	9,200	 
	 
      	 	 
      	 	 	 	 	 	
                            Sub-Total:

                          	 	 	$	122,150	 
	 
      	 	 
      	 	 	 	 	 	
                            Total

                          	 	 	$	352,341	 


                  

                

              

            

          

        

      

    

     

    Note:
*Consumable volume limited to 500 B&W and 100 colour copies/prints per
month. Excess will be billed at $0.05 per page for B&W; $0.25 per page for
colour.

     


    CONFIDENTIAL 

    
      

    

    Page 33 of 36

     

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

       

    8.
Payment Schedule and Terms

     

    A deposit
of 15% ($241,500 CDN) of
the estimated project total is to be paid upon initiation of this contract.
Detailed invoices will be submitted to Client monthly.

    


    
      	
              ·  

            	
              Monthly
      labour invoices will be issued

            


    

    
      	
              ·  

            	
              Expense
      invoices to be issued once original receipts have been collected from
      personnel.

            


    

    
      	
              ·  

            	
              Expenses
      related to courier, teleconferencing, and communication & consumables
      will be summarized on expense invoices. Original documentation will not be
      provided but is available for review for an additional fee (labour
      required to anonymize).

            


    

    
      	
              ·  

            	
              Applicable
      taxes on labor will be indicated on
invoice.

            


    

    
      	
              ·  

            	
              Payment
      terms are 30 days from receipt of
invoice.

            


    

    
      	
              ·  

            	
              2%
      per month financing fee may be applied to outstanding balance
      owing.

            


    

    
      	
              ·  

            	
              Sponsor
      authorization will be obtained if budget exceeds 10% of
      estimate.

            


    

    
      	
              ·  

            	
              The
      Client acknowledges that upon execution of the full Work Order, Allphase
      will dedicate personnel to this Project, on a full time or part time basis
      as appropriate. If after 90 days following the date of execution of this
      Work Order (exclusive of the letter of Intent provisions) the project is
      delayed for greater than 30 days for reasons beyond the control of
      Allphase (e.g. regulatory hold), if Client wishes to retain the assigned
      project team, Client agrees to pay Allphase its direct costs per assigned
      employee. This value will be calculated based on the average number of
      hours billed per individual over the preceding 3 months. This will be a
      daily calculation starting on day 31 post written notification of the
      effective date of the delay. If billable work continues during the delay
      period and the value of this work is at least equal to Allphase direct
      costs, then no additional fee will be levied. Alternately, Allphase may
      re-assign personnel to other Projects, or Client and Allphase may
      negotiate alternate arrangements to minimize the economic impact on both
      Parties.

            


    

    


    9.
Standard Practices

     

    Allphase
Clinical Research will manage the project using industry best practice and will
endeavor to perform the work at or below cost and schedule. Please be assured
that Allphase strives to economize appropriately whenever possible. The client
will be consulted regarding the possibility of deviating from the scope of work
defined within this proposal.

    


    Allphase
Standard Operating Procedures (SOP) or client SOPs can be used for this
project.

    


    Allphase
Clinical Research is an insured and incorporated company.

     


    CONFIDENTIAL 

    
      

    

    Page 34 of 36

     

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

       

    10.
Client Signatures

     

    The
details as described in the version on the Work Order referenced in the header
of this document are acceptable. Any significant change in the terms or
requirements of this Work Order will be managed in accordance with section 2.2
of the above referenced Master Services Agreement.

    


    IN
WITNESS WHEREOF, this Agreement has been executed by the Parties hereto through
their duly authorized officers on the date(s) set forth below.

    


    Agreed
and accepted

    


    YM
BioSciences Inc.

    


    
      
        	
                Signature:

              	
                  

              	 
      	
                Signature:

              	
                  

              
	 
      	 
      	 
      
	
                Date:
      December 24, 2008

              	 
      	
                Date:
      January 5, 2009

              
	 
      	 
      	 
      
	
                Name/Title:
      David Allan/Chairman & CEO

              	 
      	
                Name/Title:
      Jeff Smith/President

              
	 
      	 
      	 
      
	
                I
      have the authority to bind the corporation.

              	
                  

              	
                I
      have the authority to bind the
corporation.

              


      

    

     

    If
the details of this Work Order require further refining and the parties wish to
initiate work on the project prior to finalizing the Work Order, the Letter of
Intent of section 11of this Work Order may be executed.

     

    
      CONFIDENTIAL 

      
        

      

      Page 35 of 36

       

    

    
      
         


      

      
        
        

        
          

        

      

      
         


      

    

    


    
      
        	
                MSA#:

              	
                YMB07-MSA-17MAY2007

              	
                WO Version Code:

              	
                YMB08-WO4-15DEC2008-3.0

              
	
                Version Date:

              	
                16DEC2008

              	
                Work Order #:

              	
                WO4

              


      

    

       

    11.
Letter of Intent

     

    Further
to contact regarding the "A Phase I-II clinical study of Nimotuzumab
(TheraCIM-h-R3) in combination with external radiotherapy in stage IIb, III, IV
NSCLC. (Phase II Portion only)" study, YM
BioSciences (YMB) confirms the intent to place a contract with ALLPHASE Clinical
Research Inc.
(ALLPHASE) for clinical services in relation to this project.

    


    As the
above referenced Work Order for this project is being negotiated between YMB and
ALLPHASE, YMB authorises ALLPHASE to begin the necessary preparations for the
project upon written approval of individual tasks.

    


    YMB will
prepay 15% equal to $241,500 Canadian dollars of
the estimated project total under this Letter of Intent. It is understood that
ALLPHASE will not make any financial commitments extending beyond the above
mentioned value, before a signed Work Order has been executed by the parties.
The prepaid amount under this Letter of Intent will be reconciled against
subsequent payments for this study as agreed in the final contract.

    


    ALLPHASE
agrees that all information disclosed under this Letter of Intent is
confidential and property of YMB and agrees not to disclose or use such
information without prior written approval of YMB.

    


    In the
event that no final contract can be executed between YMB and ALLPHASE by 31
January 2009, ALLPHASE shall remit YMB the amount already paid having deducted
any fees or expenses already incurred by ALLPHASE at the time of such decision.
YMB shall have the right to audit ALLPHASE records regarding this
project.

    


    This
Letter of intent is to be signed by the parties.

    


    
      
        	
                Agreed
      and accepted

              	 
      	
                Agreed
      and accepted

              
	 	 	 
	
                YM
      BioSciences Inc.

              	 
      	
                ALLPHASE
      Clinical Research Inc.

              
	 
      	 
      	 
      
	
                Date:
      December 24, 2008

              	 
      	
                Date:
      January 5, 2009

              
	 
      	 
      	 
      
	
                Signature:

              	
                  

              	 
      	
                Signature:

              	
                  

              
	 
      	 
      	 
      
	
                Name/Title:
      David Allan/Chairman & CEO

              	 
      	
                Name/Title:
      Jeff Smith/President

              
	 
      	
                  

              	
                I
      have the authority to bind the
corporation.

              


      

    

     

    
      
        	
                Date:

              	
                  

              


      

    

     

    
      
        	
                Signature:

              	
                  

              


      

    

     

    
      
        	
                Name/Title:

              	
                  

              


      

    

     

    We have
the authority to bind the corporation.

    
       


      CONFIDENTIAL 

      
        

      

      Page 36 of 36